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Objective: In 2012, updated ASCCP management guidelines for abnormal cervical cytology recommended observation rather than immediate referral to colposcopy for low-grade abnormalities in women ages 21-24. We evaluated the impact of these guidelines on changes in colposcopy procedure rates among young women., Methods: We analyzed administrative and claims data from the largest statewide family planning program between July 2011 and June 2015. Using a difference-in-differences approach, we estimated changes in colposcopy procedure rates among women ages 21-24 years before and after the 2012 ASCCP management guidelines, relative to a comparison group of women ages 25-44., Results: Our analysis included 333,977 women from 216 primary care provider sites. After publication of the 2012 ASCCP management guidelines, colposcopy rates significantly declined from 6.70% (95% CI 6.21-7.19) to 3.94% (95% CI 3.60-4.29) among women ages 21-24 and from 4.35% (95% CI 4.03-4.67) to 3.53% (3.25-3.80) among women over 24 years. These declines correspond to a 1.93 percentage point reduction (95% CI 1.62-2.25; p < 0.001) in colposcopy rate among women 21-24 vs. over 24 years, or a two-fold relative reduction. Among women ages 21-24, colposcopy receipt was associated with speaking primarily English vs. non-English (OR 1.46, 95% CI 1.35-1.57), having a cervical cytology test within the past year vs. not (OR 1.55, 95% CI 1.44-1.66), and receiving care from a public vs. private provider (OR 1.31, 95% CI 1.06-1.62)., Conclusions: Colposcopy procedure rates among young women significantly declined following publication of the 2012 management guidelines, which has implications for reducing potential harms of overtreatment., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Over 265 000 women are living with HIV in the USA, but limited research has investigated the physical, mental and behavioural health outcomes among women living with HIV of reproductive age. Health status during the reproductive years before, during and after pregnancy affects pregnancy outcomes and long-term health. Understanding health outcomes among women living with HIV of reproductive age is of substantial public health importance, regardless of whether they experience pregnancy. The Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) study is a prospective observational cohort study designed to investigate physical and mental health outcomes of young women living with HIV as they age, including HIV disease course, engagement in care, reproductive health and choices and cardiometabolic health. We describe the HOPE study design, and characteristics of the first 437 participants enrolled as of 1 January 2024., Methods and Analysis: The HOPE study seeks to enrol and follow 1630 women living with HIV of reproductive age, including those with perinatally-acquired HIV, at 12 clinical sites across 9 US states and Puerto Rico. HOPE studies multilevel dynamic determinants influencing physical, mental and social well-being and behaviours of women living with HIV across the reproductive life course (preconception, pregnancy, post partum, not or never-pregnant), informed by the socioecological model. Key research areas include the clinical course of HIV, relationship of HIV and antiretroviral medications to reproductive health, pregnancy outcomes and comorbidities and the influence of racism and social determinants of health. HOPE began enrolling in April 2022., Ethics and Dissemination: The HOPE study received approval from the Harvard Longwood Campus Institutional Review Board, the single institutional review board of record for all HOPE sites. Results will be disseminated through conference presentations, peer-reviewed journals and lay summaries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The StRONG trial demonstrated the safety and efficacy of higher calorie refeeding (HCR) in hospitalized adolescents and young adults with malnutrition secondary to restrictive eating disorders. Here we compare refeeding outcomes in patients with atypical anorexia nervosa (atypical AN) versus anorexia nervosa (AN) and examine the impact of caloric dose., Method: Patients were enrolled upon admission and randomized to meal-based HCR, beginning 2000 kcal/day and advancing 200 kcal/day, or lower calorie refeeding (LCR), beginning 1400 kcal/day and advancing 200 kcal every other day. Atypical AN was defined as %median BMI (mBMI) > 85. Independent t-tests compared groups; multivariable linear and logistic regressions examined caloric dose (kcal/kg body weight)., Results: Among n = 111, mean ± SD age was 16.5 ± 2.5 yrs; 43% had atypical AN. Compared to AN, atypical AN had slower heart rate restoration (8.7 ± 4.0 days vs. 6.5 ± 3.9 days, p = .008, Cohen's d = -.56), less weight gain (3.1 ± 5.9%mBMI vs. 5.4 ± 2.9%mBMI, p < .001, Cohen's d = .51) and greater hypomagnesemia (29% vs. 11%, p = .03, OR = 3.29). These suboptimal outcomes were predicted by insufficient caloric dose (32.4 ± 6.9 kcal/kg in atypical AN vs. 43.4 ± 9.8 kcal/kg in AN, p < .001, Cohen's d = 1.27). For every 10 kcal/kg increase, heart rate was restored 1.7 days (1.0, 2.5) faster (p < .001), weight gain was 1.6%mBMI (.8, 2.4) greater (p < .001), and hypomagnesemia odds were 70% (12, 128) lower (p = .02)., Discussion: Although HCR is more efficacious than LCR for refeeding in AN, it contributes to underfeeding in atypical AN by providing an insufficient caloric dose relative to the greater body weight in this diagnostic group., Public Significance: The StRONG trial previously demonstrated the efficacy and safety of higher calorie refeeding in patients with malnutrition due to restrictive eating disorders. Here we show that higher calorie refeeding contributes to underfeeding in patients with atypical anorexia nervosa, including poor weight gain and longer time to restore medical stability. These findings indicate these patients need more calories to support nutritional rehabilitation in hospital., (© 2024 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Objective: We previously reported that participants with atypical anorexia nervosa (atypical AN) had higher historical and admission weights, greater eating disorder psychopathology, but similar rates of amenorrhea and weight suppression at baseline as compared to anorexia nervosa (AN); here, we compare 1-year outcomes., Method: Weight, % median body mass index (%mBMI), Eating Disorder Examination Questionnaire (EDE-Q) scores, resumption of menses, and rehospitalizations were examined at 3, 6, and 12 months post-discharge. Analyses (N = 111) compared changes in %mBMI, weight suppression, and EDE-Q scores over time between atypical AN and AN., Results: Among the participants (48 atypical AN, 63 AN), both groups gained weight but those with atypical AN had lower gains than those with AN in %mBMI (p = .02) and greater weight suppression (p = .002) over time. EDE-Q scores improved over time, independent of weight suppression, with no significant difference between atypical AN and AN. Groups did not differ by rates of resumption of menses (80% atypical AN, 76.9% AN) or rehospitalization (29.2% atypical AN, 37.9% AN). Greater weight suppression predicted longer time to restore menses and more days of rehospitalization., Discussion: Individuals with atypical AN regained a smaller proportion of body mass and were more weight suppressed over time. Change in eating disorder cognitions, resumption of menses, and rehospitalization rates at 1-year follow-up did not differ between groups. There was no significant difference in weight suppression between groups for those who were psychologically improved at 12 months. Findings highlight limitations in our understanding of weight recovery in atypical AN. New metrics for recovery are urgently needed., Public Significance: Little is known about outcome in atypical anorexia nervosa (atypical AN). We examined recovery metrics in young people with atypical AN and anorexia nervosa (AN) 1 year after medical hospitalization. Individuals with atypical AN showed slower weight gain and remained further from their pre-illness weight. There were no differences in the rates of psychological recovery, resumption of menses, or rehospitalization. New metrics are needed to assess recovery in atypical AN., (© 2023 Wiley Periodicals LLC.)

Abstract: This Research Letter summarizes all updates to the 2019 Guidelines through September 2023, including: endorsement of the 2021 Opportunistic Infections guidelines for HIV+ or immunosuppressed patients; clarification of use of human papillomavirus testing alone for patients undergoing observation for cervical intraepithelial neoplasia 2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged 25 years and older screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for cervical intraepithelial neoplasia 2+, 3 negative human papillomavirus tests or cotests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of postcolposcopy management of minimally abnormal results., Competing Interests: The following listed authors have conflicts of interest: The other authors have declared they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASCCP.)

The burden of cervical cancer is disproportionately distributed globally, with the vast majority of cases occurring in low- and middle-income countries. Women with human immunodeficiency virus (HIV) (WWH) are at increased risk of human papillomavirus (HPV) infection and cervical cancer as compared to HIV-negative individuals. HPV vaccination remains a priority in regions with a high burden of cervical cancer and high HIV prevalence. With HPV vaccines becoming more accessible, optimal use beyond the initial World Health Organization-recommended target population of 9 to 14-year-old girls is an important question. In March 2022, a group of experts in epidemiology, immunology, and vaccinology convened to discuss the state-of-the-science of HPV vaccination in WWH. This report summarizes the proceedings: review of HIV epidemiology and its intersection with cervical cancer burden, immunology, HPV vaccination including reduced-dose schedules and experience with other vaccines in people with HIV (PWH), HPV vaccination strategies and knowledge gaps, and outstanding research questions. Studies of HPV vaccine effectiveness among WWH, including duration of protection, are limited. Until data from ongoing research is available, the current recommendation for WWH remains for a multi-dose HPV vaccination regimen. A focus of the discussion included the potential impact of HIV acquisition following HPV vaccination. With no data currently existing for HPV vaccines and limited information from non-HPV vaccines, this question requires further research. Implementation research on optimal HPV vaccine delivery approaches for WWH and other priority populations is also urgently needed., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AMD reports participation in advisory boards for Sanofi, Bioaster, Speranza and ACM Biolabs, and research grants from GlaxoSmithKline, Moderna, and Roche, outside the submitted work. ABM reports personal fees from Merck & Co. global advisory board honorarium, outside the submitted work. GL is an employee of Merck & Co. NM is a recipient of an Investigator Initiated Grant evaluating ‘Immunogenicity of HPV vaccine among HIV infected adolescents’, outside the submitted work. JMP reports grants and personal fees from Merck & Co., from Vir Biotechnologies, from Antiva Biosciences, from Roche Diagnostics, and other from Virion Therapeutics, outside the submitted work. JS reports participation to DSMB for NCT04508309 and the India/IARC Gardasil trial. SAM reports grants from Bill & Melinda Gates Foundation, Pfizer, GlaxoSmithKline, Minervax and Sanofi, outside the submitted work. SP reports personal fees from Merck & Co. global advisory board honorarium, and personal fees from Sanofi, Inovio, Merck & Co., Janssen, Moderna, Valneva, Codagenix, Pfizer, VaxArt, Meissa, Vaxinnity, Rational, and AstraZeneca, outside the submitted work. RB reports grants from National Institutes of Health and Bill & Melinda Gates Foundation and non-financial support from Regeneron Pharmaceutical, outside the submitted work. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objectives: A single dose of human papillomavirus (HPV) vaccine would simplify logistics and reduce costs of vaccination programs worldwide. We conducted a phase IIa trial to determine the stability of HPV type-specific antibody responses after a single dose of the nonavalent HPV vaccine, Gardasil9., Methods: Two hundred-and-one healthy 9 to 11-year-old girls and boys were enrolled at 2 centers in the United States to receive a prime dose of the nonavalent vaccine at baseline, a delayed dose at month 24, and an optional third dose at month 30. Blood samples were collected to measure HPV type-specific antibodies at baseline and at 6, 12, 18, 24, and 30 months after the prime dose. The primary outcomes were serum HPV16 and HPV18 antibody responses., Results: In both girls and boys, geometric mean concentrations of HPV16 and HPV18 antibodies increased at 6 months, declined between months 6 to 12, and then remained stable and high (at 20- and 10-times those at baseline for HPV16 and HPV18, respectively) throughout months 12, 18, and 24 (prebooster) visits. Both HPV16 and HPV18 antibody responses demonstrated anamnestic boosting effect at 30-months after the delayed (24-month) booster dose., Conclusions: A single dose of the nonavalent HPV vaccine induced persistent and stable HPV16 and HPV18 antibody responses up to 24 months. This study contributes important immunogenicity data to inform feasibility of the single dose HPV vaccination paradigm. Further research is needed to assess the long-term antibody stability and individual clinical and public health benefit of the single dose schedule., (Copyright © 2023 by the American Academy of Pediatrics.)

Cervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic - especially in vaccination, self-administered testing, and coordinated mobilization on a global scale - may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally., Competing Interests: RL received a grant from NIH NCI 1K08CA271949-01. The author has no other competing interests to declare, SF received grants from NCI/NIH and the Society to Improve Diagnosis in Medicine, and has received royalties from Uptodate. They have received payment for post-graduate talks at the Indian Health Service and Harvard Medical School, and for a community talk at Team Maureen. They received support for attending meetings of the ASCCP and the American Cancer Society. The author participated on the Mitre CDC sponsored initiative to integrate cervical cancer screening results into EHR and the American Cancer Society Advisory Committee ACS Cervical Cancer Roundtable. They are a Board Member of the IPVS and co-chair for ACS. The author has no other competing interests to declare, YW is a committee member for policy as part of IPVS. The author has no other competing interests to declare, AM has received from consulting fees from the Merck Advisory Board. The author participated on a Data Safety Monitoring Board/Advisory Board for CVIA 087 DSMB funded by PATH, and is an International Papillomavirus Society Board member. The author has no other competing interests to declare, AG has received grants and consulting fees from Merck & Co, Inc No other competing interests to declare, Sd is a consultant at the National Cancer Institute (NIH, United States). No other competing interests to declare, AK has received grants from the EU EUROSTARS Program; has received payment for consultation from Paul-Ehrlich Gesellschaft e.V; has been issued with patent WO 2020/161285 A1 (Inventor); member of the Data Safety Monitoring Board/Advisory Board for the German Cancer Research Center (DKFZ). No other competing interests to declare, SL, FG, NB No competing interests declared, KC member of Hong Kong SAR cancer coordinating committee (advisory board ) and the HK SAR cancer expert working group; President of the Hong Kong College of Obstetricians & Gynaecologists; council member of the Asian Society of Gynaecological Oncology (ASGO); board member for the Asia-Oceania Research Organisation in Genital Infection and Neoplasia. No other competing interests to declare, MS Has received consulting fees from MSD Merck UK; has participated in a Global Advisory Board for HPV vaccines for Merck. No other competing interests to declare, JB has received donated HPV tests and swabs for validation and research from Cepheid, Abbott, Seegene, Roche, AusDiagnostics, BD, and Copan. No other competing interests to declare, JP has received grants from Merck & Co., Roche Diagnostics, Antiva Biosciences, Vir Biotechnologies and Virion Therapeutics; has received consulting fees from Merck & Co., Roche Diagnostics, Antiva Biosciences and Vir Biotechnologies; has received payment for consultation from Gilead Pharmaceuticals, Merck & Co. and Janssen Pharmaceuticals; has received support for attending meetings from Merck & Co. and Roche Diagnostics; participates on the Data Safety Monitoring Board/Advisory Board for the IPVS; is Chair of the International HPV Awareness Day Campaign; has stock or stock options in Virion Therapeutics; has received resources/services from Atila Biosystems. No other competing interests to declare, SG has received consulting fees and lecture fees from Merck; has participated in an advisory Board for Merck; is President of the International Papillomavirus Society; has received an education grant for a study of HPV in young women. No other competing interests to declare

Background and Objectives: Fluid shifts have been ascribed to central diabetes insipidus in patients with anorexia nervosa hospitalized for refeeding. Recent data, however, suggest that vasopressin production is not dysregulated in this population. Our objective was to describe the trajectory of fluid imbalances in relationship to kidney function, electrolyte disturbances, and acid/base balance during refeeding., Methods: A retrospective review of daily fluid balance and biochemical values was performed in 70 sequential unique patients admitted to University of California at Los Angeles Hospital Medical Stabilization Program for Eating Disorders from December 2018 to November 2020., Results: Participants (2 males/68 females) were between 10 and 24 years of age and with a median body mass index of 16.1 (14.3, 18.1) kg/m 2 . A severe negative fluid balance (>-900 ml/day) was observed in 80% of patients at some point during hospitalization. Serum sodium concentrations were normal on admission and remained stable during refeeding. Serum bicarbonate concentrations were 25 ± 1 mEq/dl on admission and increased above the normal range in 31% of patients. Metabolic alkalosis was inversely associated with the development of a negative fluid balance. Estimated glomerular filtration rate was impaired in 54% of patients, improved with refeeding, and was not associated with the development of a severe negative fluid balance or metabolic alkalosis., Discussion: Chronic energy deprivation alters the physiology of renal fluid and bicarbonate handling in ways that are independent of vasopressin and glomerular filtration. Further studies are warranted to understand the renal adaptations that occur during energy restriction and subsequent refeeding., Public Significance: Massive urinary fluid losses occur in patients with restrictive eating disorders hospitalized for refeeding. In addition, many patients have impaired renal bicarbonate excretion. These findings suggest that chronic energy deprivation impairs the kidney's ability to handle the shifts in fluid and acid/base balance that occur when appropriate oral nutrition is re-introduced., (© 2022 Wiley Periodicals LLC.)

Background: Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention., Methods: We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology., Results: In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+., Conclusions: Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk., Competing Interests: Potential conflicts of interest. A. P. O. reports grants made to her institutions from AMC, grant no. 2UM1CA121947 and an UPR/MDACC Partnership grant no. 2U54CA096297 for time and effort support to the present manuscript. She reports NIH grants not related to the current work. She reports consulting fees and payment for lectures from Merck and Co. R. K. was supported by the Canadian Institutes of Health Research (CIHR) for the present manuscript. A. d. P. shared data from the EVVA study for this manuscript. The EVVA study was supported by the CIHR, and the AIDS and Infectious Diseases Network of Fonds de Recherche du Quebec Sante. Payments were made to A. d. P.’s institution. J. M. P. reports grants and personal fees from Merck and Co.; consulting fees from Vir Biotechnology, Antiva Biosciences, and Virion Therapeutics; personal fees Janssen Pharmaceuticals; stock or stock options from Virion Therapeutics and Vir Biotechnology (outside the submitted work); and a leadership role in the International Papillomavirus Society. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized., Methods: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants., Results: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection., Conclusions: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection., Competing Interests: Potential conflicts of interest. A. R. G. received support from Merck & Co and Moderna, outside the submitted work, and reports consulting fees from Merck & Co. G. D. received support to her institution from the National Institutes of Health (NIH) for this work. N. A. H. received a grant to her institution from NIH for this work. M. F. S. v. d. L. has served on an advisory board for Merck & Co. K. N. received a Miguel Servet II senior researcher grant contract (CPII18/00033) from the Instituto de Salud Carlos III (Madrid, Spain), outside the submitted work. J. B. received financial compensation for lectures, consultancy work, educational activities from Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare and received support for attending meetings from Gilead Sciences, outside the submitted work. M. L. G. received support from National Institute of Dental and Craniofacial Research for and outside the submitted work; has received research funding from Genocea Biosciences, Bristol-Myers Squibb, Genentech, Kur, Cullinan Labs, and Agenus; served as a consultant for Istari Oncology, LLX Solutions, Kura Oncology, Mirati Therapeutics, BioNtech, Bristol-Myers Squibb, Bicara Therapeutics, Bayer Healthcare Pharmaceutics, Genocea Biosciences, Shattucks Labs, EMD Serono, Debiopharm, Merck & Co, Ipsen Biopharmaceuticals, Gilead Sciences, and Coherus; served a speaker/preceptorship role for OncLive and Roche Scientific; received support for attending meetings from American Association for Cancer Research (AACR); has an issued patent as sponsor-investigator for pNGVL4a-Sig/E7(detox)/HSP70 plasmid DNA for a clinical protocol entitled “An open-label phase one study of the safety with stage III or IV HPV16-positive head and neck squamous cell carcinoma”; has pending patents for “Oral HPV infection detection for oral cancer screening and diagnosis” and “HPV mRNA detection on oral cytology specimens for diagnosis and screening for oral cancer”; served on advisory committees for Seagen, Sensei Biotherapeutics, SQZBiotech, BioMimetix and Kura; and has stock options for Sensei. A. G. N. received grants from National Institute of Allergy and Infectious Diseases (NIAID) and the National Cancer Institute (NCI), NIH, and Merck & Co, awarded to his institution and related to the submitted work; received grants from NCI, NIH, awarded to his institution, outside the submitted work; received support for attending meetings (payment for hotel at conference) from the European Research Organisation on Genital Infection and Neoplasia; and received donated swabs and vials for research from COPAN Diagnostics. R. G. N. received funding from NCI, NIH (grant K07CA225403), paid to her institution. E. Y. received to her institution, for this work, in support from subawards from amfAR, The Foundation for AIDS Research (grants 108520-52-IGTA and 108893-55-IPTA), with funds provided by Life Ball and Verein Aids Life (AIDS LIFE). The Asia Pacific HIV Research Collaboration is an initiative of TREAT Asia, a program of amfAR, The Foundation for AIDS Research, with support from the NIAID, NIH, as part of the International Epidemiologic Databases to Evaluate AIDS (IeDEA). These subgrants were supported with funds provided by NIH cooperative agreement 5U01AI0699007-07 and a supplement to NIH cooperative agreement 5U01AI0699007-08. J. M. M. received research grants from Gilead to his institution for the present work and personal consulting fees from Gilead, Merck & Co, and ViiV. JJO received funds both to himself and to his institution from Australian National Health and Medical Research Council, outside the submitted work; served as Board Director of Australian Society of HIV, viral hepatitis and sexual heath medicine (ASHM), Australian Federation of AIDS Organizations (AFAO). N. S. received personal consulting fees from ViiV Healthcare and honoraria from Gilead Sciences. D. J. W. received funding from the NCI, NIH (R01CA169508-01A1 [principal investigator (PI), D. J. W.] and 5UM1AI035043-23 (PI, G. D.; site PI, D. J. W.; both studies: data collection, specimen processing, laboratory tests). J. M. P. reports grants or contracts paid to the institution from Merck and Co, outside the submitted work; consulting fees paid to self from Vir Biotechnologies and Antiva Biosciences; payment or honoraria from Merck and Co; support for attending meetings and/or travel paid to self from Merck and Co; and stock or stock options from Virion Therapeutics and Vir Biotechnology. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We describe trends in prevalence and identify factors associated with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), syphilis, and Trichomonas vaginalis (TV) diagnosed in pregnancy among US people with human immunodeficiency virus (PWH) and evaluate associations of sexually transmitted infections (STIs) with preterm birth (PTB)., Methods: We included pregnant PWH enrolled in the Surveillance Monitoring for ART Toxicities dynamic cohort of the Pediatric HIV/AIDS Cohort Study network who delivered between 2010 and 2019. Multivariable log-binomial or Poisson generalized estimating equation models were used to estimate the association of calendar year with each STI, controlling for confounders; the association of demographic and clinical factors with each STI; and the association of each STI with PTB., Results: The sample included 2241 pregnancies among 1821 PWH. Median age at delivery was 29.2 years; 71% of participants identified as Black or African American. STI prevalence was: CT 7.7%, NG 2.3%, syphilis 2.4%, and TV 14.5%; 30% had unknown TV status. There were no temporal changes in STI prevalence. Younger age and initial HIV viral load ≥400 copies/mL were associated with increased risk of CT, NG, and TV. Recreational substance use was a risk factor for NG, syphilis, and TV. No STI was associated with PTB., Conclusions: Unlike nationwide trends, no changes in STI prevalence during the study period were observed. The large proportion with unknown TV status underscores the need for increased adherence to screening guidelines. STIs diagnosed during pregnancy in PWH were not associated with risk of PTB., Competing Interests: Potential conflicts of interest. K. M. P. reports funding paid to the institution from the National Institutes of Health, outside the submitted work. E. G. C. reports payment for expert testimony from Brown & James, P.C. (paid to self) and stock or stock options from AbbVie (to spouse). L. Y. reports grant to institution from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, and Friends of Prentice, outside the submitted work. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The female reproductive tract, similar to other mucosal sites, harbors a specific microbiome commonly dominated by Lactobacillus species (spp.), which has an essential role in maintaining health and homeostasis. Increasing evidence shows that genital tract dysbiosis and/or specific bacteria and cytokines might have an active role in the development and/or progression of HPV infection and cervical intra-epithelial neoplasia (CIN) and as a result cervical cancer. Cross-sectional and longitudinal studies reported that Lactobacillus spp. depletion increases with severity of CIN and that this may negatively affect disease regression rates. It is plausible that Lactobacillus deplete microbiome composition may lead to a pro-inflammatory environment that can increase malignant cell proliferation and HPV E6 and E7 oncogene expression. Future longitudinal cohorts and mechanistic experiments on HPV transfected cells models will further permit exploration of the impact of Lactobacillus spp. on HPV infection., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence., Methods: We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples., Results: We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here., Conclusions: Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies., (© 2022. The Author(s).)

Purpose: Among complications of malnutrition secondary to anorexia nervosa (AN) or atypical anorexia nervosa (AAN), renal impairment remains poorly elucidated. Evaluating renal function in hospitalized pediatric patients with AN and AAN undergoing refeeding will yield important information to guide clinicians in screening and managing renal dysfunction in this population., Methods: This is a secondary analysis of data from the Study of Refeeding to Optimize Inpatient Gains trial, a multicenter randomized clinical trial comparing higher calorie refeeding versus lower calorie refeeding in 120 adolescents and young adults hospitalized with medical instability secondary to AN or AAN. Baseline disease characteristics were obtained. Vital sign measurements, weight, electrolytes, and fluid status were evaluated daily to ascertain medical stability. Renal function on admission and throughout hospitalization was quantified using daily creatinine measurement and calculation of the estimated glomerular filtration rate (eGFR) using the modified Schwartz equation. Regression analysis and mixed linear models were utilized to evaluate factors associated with eGFR., Results: Of the 111 participants who completed treatment protocol, 33% had a baseline eGFR less than 90, suggesting renal impairment. Patients who experienced more rapid weight loss and more severe bradycardia were more likely to have low admission eGFR. While eGFR improved during refeeding, eGFR change by day based on refeeding treatment assignment did not reach statistical significance (95% confidence interval, -1.61, 0.15]; p = .095)., Discussion: Renal impairment is evident on admission in a significant number of adolescents and young adults hospitalized with AN and AAN. We demonstrate that short-term medical refeeding yields improvement in renal function., (Copyright © 2022 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Current cervical cancer screening guidelines recommend 3-year screening intervals, in contrast to the previous recommendation of annual screening, to prevent over screening and overtreatment. We evaluated the impact of viewing a tablet-based educational tool prior to seeing a clinician on young women's knowledge and understanding of cervical cancer screening, HPV vaccination follow-up of abnormal pap smears, and comfort in communicating with their providers., Methods: This cross-sectional study was part of a cluster-randomized study of fourteen primary care clinics from January 2015 to December 2016. We developed the cervical cancer education tool in English and Spanish using a community-based approach that included formative work and cognitive interviewing. Clinics were randomized to use the intervention (tablet-based patient education tool) or to participate as a control group. We administered surveys to a convenience sample of 229 English- or Spanish-speaking women aged 19 to 35 years in these clinics. We used descriptive analyses and logistic regression models with cluster-robust standard errors to compare differences among the two groups., Results: Compared to women seen in control clinics, women seen in intervention clinics demonstrated greater knowledge regarding human papilloma virus (HPV (p = 0.004) and understanding (p < 0.001) of cervical cancer screening. Comfort in communicating with providers was not statistically different (p = 0.053). Women in the intervention group felt that the tool helped them understand that an abnormal Pap smear does not require immediate treatment (61.5%)., Conclusion: Innovative online patient education that is offered prior to patients' interaction with their clinicians can improve their knowledge about cervical cancer prevention and treatment., (© 2022. The Author(s).)

Objective: The US screening and management guidelines for cervical cancer are based on the absolute risk of precancer estimated from large clinical cohorts and trials. Given the widespread transition toward screening with human papillomavirus (HPV) testing, it is important to assess which additional factors to include in clinical risk assessment to optimize management of HPV-infected women., Materials and Methods: We analyzed data from HPV-infected women, ages 30-65 years, in the National Cancer Institute-Kaiser Permanente Northern California Persistence and Progression study. We estimated the influence of HPV risk group, cytology result, and selected cofactors on immediate risk of cervical intraepithelial neoplasia grade 3 or higher (CIN 3+) among 16,094 HPV-positive women. Cofactors considered included, age, race/ethnicity, income, smoking, and hormonal contraceptive use., Results: Human papillomavirus risk group and cytology test result were strongly correlated with CIN 3+ risk. After considering cytology and HPV risk group, other cofactors (age, race/ethnicity, income, smoking, and hormonal contraceptive use) had minimal impact on CIN 3+ risk and did not change recommended management based on accepted risk thresholds. We had insufficient data to assess the impact of long-duration heavy smoking, parity, history of sexually transmitted infection, or immunosuppression., Conclusions: In our study at the Kaiser Permanente Northern California, the risk of CIN 3+ was determined mainly by HPV risk group and cytology results, with other cofactors having limited impact in adjusted analyses. This supports the use of HPV and cytology results in risk-based management guidelines., Competing Interests: The National Cancer Institute (including all NCI-affiliated authors) receives cervical screening results at reduced or no cost from commercial research partners (Qiagen, Roche, BD, MobileODT, Arbor Vita) for independent evaluations of screening methods and strategies, A.-B.M. is a Merck and GSK, Advisory Board member. P.E.C. has received human papillomavirus tests and assays at a reduced or no cost from Roche, Becton Dickinson, Arbor Vita Corporation, and Cepheid for research. A.H. has received reagents for free from Roche, Denmark, for an unrelated study. The other authors have declared they have no conflicts of interest., (Copyright © 2022, ASCCP.)

Background: Developing a causal graph is an important step in etiologic research planning and can be used to highlight data flaws and irreparable bias and confounding. As a case study, we consider recent findings that suggest human papillomavirus (HPV) vaccine is less effective against HPV-associated disease among girls living with HIV compared to girls without HIV., Objectives: To understand the relationship between HIV status and HPV vaccine effectiveness, it is important to outline the key assumptions of the causal mechanisms before designing a study to investigate the effect of the HPV vaccine in girls living with HIV infection., Methods: We present a causal graph to describe our assumptions and proposed approach to explore this relationship. We hope to obtain feedback on our assumptions before data analysis and exemplify the process for designing causal graphs to inform an etiologic study., Conclusion: The approach we lay out in this paper may be useful for other researchers who have an interest in using causal graphs to describe and assess assumptions in their own research before undergoing data collection and/or analysis., (Copyright © 2022. Published by Elsevier Inc.)

Background: Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines., Methods: We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls., Results: Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment., Conclusions: Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus-enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence., (© 2021. The Author(s).)

Competing Interests: Conflict of interest: The following listed authors have no conflicts of interest to disclose: Drs. Perkins, Chelmow, Garcia, Kim, Nayar, Saraiya, and Sawaya. The following listed authors have conflicts of interest:

We examined reporting agreement of oral, vaginal, and anal sex in adolescents and young adults living with perinatally-acquired HIV and those perinatally HIV-exposed and uninfected in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (AMP) and AMP Up studies. Agreement between fixed constructs (e.g., age at first sex) and prevalence of logical inconsistencies (e.g., reclaimed virginity status) over time were assessed. Internal consistency was also examined using an attention check question and questions regarding condom use in the prior three months. Those who reported having anal sex in adolescence had a higher proportion of inconsistent responses compared to vaginal and oral sex measures. At their most recent survey, 84% of young adults correctly answered an attention check question and 74% agreed within the survey on condom use in the prior three months. In bivariate analyses, HIV status was not associated with responding inconsistently. Increased time between surveys, male sex, and younger age at first survey were associated with multiple measures of inconsistency over time, while lower cognitive scores, having less than a high school diploma, and negatively answering post-survey acceptability questions were associated with incorrectly answering an attention check question., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study examined associations of self-regulatory behavior and cognitive functioning with substance use (SU) to inform interventions for youth with perinatal HIV infection (YPHIV) or exposure but uninfected (YPHEU). Youth aged 7-15 years (YPHIV, n = 390; YPHEU, n = 211) were followed longitudinally with cognitive testing and behavioral questionnaires including self-report of alcohol, marijuana, tobacco, and other SU. Cox proportional hazards analyses were used to examine correlates of initiating each substance for those without prior use at baseline and generalized estimating equation analyses were used to address associations of cognitive/behavioral measurements with SU prevalence for the entire sample. Lower self-reported self-regulation skills, but higher cognitive functioning abilities, were associated with initiation and prevalent use of alcohol and marijuana regardless of HIV status. Our findings suggest SU screening tools and self-regulation interventions developed for general adolescent populations should be implemented for those with PHIV, who may be at heightened risk for SU-related health consequences., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Introduction: This study sought to determine whether a provider mobile phone application, used with or without a patient educational tool accessed on a computer tablet, would promote adherence to guidelines for cervical cancer screening and management of abnormal cytology in young women., Methods: The study was conducted as a prospective cohort study in which 14 Family Planning, Access, Care, and Treatment provider clinics were randomized to 1 of 2 arms: (1) provider mobile phone application only or (2) provider mobile phone application plus patient educational tool. The provider mobile phone application gave information to providers regarding cervical cancer screening and management of abnormal cytology. The patient educational tool accessed on a computer tablet was a patient-centered educational tool. Each arm was compared with clinic control groups (no intervention) in a 2:1 ratio (control:intervention). Claims data were used to calculate and compare 18-month cytology (Pap) and colposcopy rates before the intervention and during the 18 months using the Poisson mixed-effect regression model. A sensitivity analysis examined the differences in the rate of change between each arm and controls. The study took place between July 2015 and December 2016, and analysis was performed in 2019., Results: The clinics randomized to the provider mobile phone application plus patient educational tool arm and their control group achieved similar 18-month Pap rates (0.52, 95% CI=0.37, 0.74 and 0.68, 95% CI=0.53, 0.86, respectively) as well as the provider mobile phone application arm and their control group (0.44, 95% CI=0.33, 0.58 and 0.41, 95% CI=0.34, 0.51; p-values >0.1). In the sensitivity analysis, the difference in the rate of change in Pap rates for the provider mobile phone application plus patient educational tool arm and their control group before and during the intervention was -0.22 and -0.09, respectively (p=0.02), but no differences were seen between the provider mobile phone application arm and their control group. No significant changes were observed for colposcopy rates., Conclusions: Providing clinicians and patients with information on guidelines had no demonstrable effect on 18-month Pap and colposcopy rates in the regression model; however, results from the sensitivity analysis for the patient educational tool were encouraging., Trial Registration: This study is registered at www.clinicaltrials.gov NCT02270021., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: We recently reported the short-term results of this trial revealing that higher-calorie refeeding (HCR) restored medical stability earlier, with no increase in safety events and significant savings associated with shorter length of stay, in comparison with lower-calorie refeeding (LCR) in hospitalized adolescents with anorexia nervosa. Here, we report the 1-year outcomes, including rates of clinical remission and rehospitalizations., Methods: In this multicenter, randomized controlled trial, eligible patients admitted for medical instability to 2 tertiary care eating disorder programs were randomly assigned to HCR (2000 kcals per day, increasing by 200 kcals per day) or LCR (1400 kcals per day, increasing by 200 kcals every other day) within 24 hours of admission and followed-up at 10 days and 1, 3, 6, and 12 months post discharge. Clinical remission at 12 months post discharge was defined as weight restoration (≥95% median BMI) plus psychological recovery. With generalized linear mixed effect models, we examined differences in clinical remission over time., Results: Of 120 enrollees, 111 were included in modified intent-to-treat analyses, 60 received HCR, and 51 received LCR. Clinical remission rates changed over time in both groups, with no evidence of significant group differences ( P = .42). Medical rehospitalization rates within 1-year post discharge (32.8% [19 of 58] vs 35.4% [17 of 48], P = .84), number of rehospitalizations (2.4 [SD: 2.2] vs 2.0 [SD: 1.6]; P = .52), and total number of days rehospitalized (6.0 [SD: 14.8] vs 5.1 [SD: 10.3] days; P = .81) did not differ by HCR versus LCR., Conclusions: The finding that clinical remission and medical rehospitalization did not differ over 1-year, in conjunction with the end-of-treatment outcomes, support the superior efficacy of HCR as compared with LCR., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Le Grange receives royalties from Guilford Press and Routledge and is codirector of the Training Institute for Child and Adolescent Eating Disorders; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Importance: The standard of care for refeeding inpatients with anorexia nervosa, starting with low calories and advancing cautiously, is associated with slow weight gain and protracted hospital stay. Limited data suggest that higher-calorie refeeding improves these outcomes with no increased risk of refeeding syndrome., Objective: To compare the short-term efficacy, safety, and cost of lower-calorie vs higher-calorie refeeding for malnourished adolescents and young adults with anorexia nervosa., Design, Setting, and Participants: In this multicenter randomized clinical trial with prospective follow-up conducted at 2 inpatient eating disorder programs at large tertiary care hospitals, 120 adolescents and young adults aged 12 to 24 years hospitalized with anorexia nervosa or atypical anorexia nervosa and 60% or more of median body mass index were enrolled from February 8, 2016, to March 7, 2019. The primary analysis was a modified intent-to-treat approach., Interventions: Higher-calorie refeeding, beginning at 2000 kcal/d and increasing by 200 kcal/d vs lower-calorie refeeding, beginning at 1400 k/cal and increasing by 200 kcal every other day., Main Outcomes and Measures: Main outcomes were end-of-treatment outcomes; the primary end point of this trial will be clinical remission over 12 months. Short-term efficacy was defined a priori as time to restore medical stability in the hospital, measured by the following 6 indices: 24-hour heart rate of 45 beats/min or more, systolic blood pressure of 90 mm Hg or more, temperature of 35.6 °C or more, orthostatic increase in heart rate of 35 beats/min or less, orthostatic decrease in systolic blood pressure of 20 mm Hg or less, and 75% or more of median body mass index for age and sex. The prespecified safety outcome was incidence of electrolyte abnormalities; cost efficacy was defined as savings associated with length of stay., Results: Because 9 participants withdrew prior to treatment, the modified intention-to-treat analyses included 111 participants (93%; 101 females [91%]; mean [SD] age, 16.4 [2.5] years). Higher-calorie refeeding restored medical stability significantly earlier than lower-calorie refeeding (hazard ratio, 1.67 [95% CI, 1.10-2.53]; P = .01). Electrolyte abnormalities and other adverse events did not differ by group. Hospital stay was 4.0 days shorter (95% CI, -6.1 to -1.9 days) among the group receiving higher-calorie refeeding, which was associated with a savings of $19 056 (95% CI, -$28 819 to -$9293) in hospital charges per participant., Conclusions and Relevance: In the first randomized clinical trial in the US to compare refeeding approaches in patients with anorexia nervosa and atypical anorexia nervosa, higher-calorie refeeding demonstrated short-term efficacy with no increase in safety events during hospitalization., Trial Registration: ClinicalTrials.gov Identifier: NCT02488109.

Persistent human papillomavirus (HPV) infections is necessary for the development of cervical cancers. Consequently, understanding the biologic mechanisms resulting in clearance is key in cancer prevention. Similar to other mucosal sites, it is expected that the local microbiome plays a significant role in shaping the immune response responsible for HPV clearance. Using cervical wash repository samples from a prospective study of HPV in women, this study investigates the microbiome and its associated inflammatory milieu during HPV 16 pre-acquisition, persistence and clearance states. For comparison, samples from women with no history of HPV ever during the study period were selected. We showed that 9 of 13 inflammatory cytokines were found to be significantly increased in the immediate post-clearance visit compared to the pre-acquisition or infection visits. Gardnerella vaginalis was associated with higher levels of inflammatory cytokines. Women with no history of HPV infection had similar cytokine profiles as those with HPV 16 post-clearance. This in vivo study documented an immune response shortly after HPV 16 clearance. G. vaginalis appeared to be involved in shaping this immune response. The appearance of G. vaginalis may have resulted from a shift from anti-microbial to anti-viral immune response with loss of bacterial control. The similar high levels of cytokines seen in women with no history of HPV suggest that a certain level of inflammatory surveillance is required to maintain an HPV negative state. This data may inform therapies such as probiotics or pro-inflammatory agents for treatment of persistent HPV., (Copyright © 2020 Moscicki, Shi, Huang, Barnard and Li.)

Introduction: Salivary metabolite profiles are altered in adults with HIV compared to their uninfected counterparts. Less is known about youth with HIV and how oral disorders that commonly accompany HIV infection impact salivary metabolite levels., Objective: As part of the Adolescent Master Protocol multi-site cohort study of the Pediatric HIV/AIDS Cohort Study (PHACS) network we compared the salivary metabolome of youth with perinatally-acquired HIV (PHIV) and youth HIV-exposed, but uninfected (PHEU) and determined whether metabolites differ in PHIV versus PHEU., Methods: We used three complementary targeted and discovery-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflows to characterize salivary metabolite levels in 20 PHIV and 20 PHEU youth with and without moderate periodontitis. We examined main effects associated with PHIV and periodontal disease, and the interaction between them., Results: We did not identify differences in salivary metabolite profiles that remained significant under stringent control for both multiple between-group comparisons and multiple metabolites. Levels of cadaverine, a known periodontitis-associated metabolite, were more abundant in individuals with periodontal disease with the difference being more pronounced in PHEU than PHIV. In the discovery-based dataset, we identified a total of 564 endogenous peptides in the metabolite extracts, showing that proteolytic processing and amino acid metabolism are important to consider in the context of HIV infection., Conclusion: The salivary metabolite profiles of PHIV and PHEU youth were overall very similar. Individuals with periodontitis particularly among the PHEU youth had higher levels of cadaverine, suggesting that HIV infection, or its treatment, may influence the metabolism of oral bacteria.

Microorganisms play critical roles in human health and disease. They live in diverse communities in which they interact synergistically or antagonistically. Thus for estimating microbial associations with clinical covariates, such as treatment effects, joint (multivariate) statistical models are preferred. Multivariate models allow one to estimate and exploit complex interdependencies among multiple taxa, yielding more powerful tests of exposure or treatment effects than application of taxon-specific univariate analyses. Analysis of microbial count data also requires special attention because data commonly exhibit zero inflation, i.e., more zeros than expected from a standard count distribution. To meet these needs, we developed a Bayesian variable selection model for multivariate count data with excess zeros that incorporates information on the covariance structure of the outcomes (counts for multiple taxa), while estimating associations with the mean levels of these outcomes. Though there has been much work on zero-inflated models for longitudinal data, little attention has been given to high-dimensional multivariate zero-inflated data modeled via a general correlation structure. Through simulation, we compared performance of the proposed method to that of existing univariate approaches, for both the binary ("excess zero") and count parts of the model. When outcomes were correlated the proposed variable selection method maintained type I error while boosting the ability to identify true associations in the binary component of the model. For the count part of the model, in some scenarios the univariate method had higher power than the multivariate approach. This higher power was at a cost of a highly inflated false discovery rate not observed with the proposed multivariate method. We applied the approach to oral microbiome data from the Pediatric HIV/AIDS Cohort Oral Health Study and identified five (of 44) species associated with HIV infection., (© The Author 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16-26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.

Background: Small studies reported poor post-partum outcomes among young women living with perinatal HIV infection who are now ageing into adulthood and becoming pregnant. For targeted clinical intervention, we sought to identify women in this population at risk of poor post-partum virological control., Methods: We abstracted data on pregnancy history for women living with perinatal HIV infection in the Pediatric HIV/AIDS Cohort Study-AMP Up protocol, a prospective study of young adults living with perinatal HIV from 14 sites in the USA. Linear models with generalised estimating equations described trends in HIV viral load through 1 year post-pregnancy by pregnancy outcome. We used group-based trajectory modelling to identify viral load trajectory groups in the first post-partum year after livebirths. We then compared sociodemographic and clinical factors across identified groups. We defined viraemia as 400 copies per mL or more., Findings: Between April 15, 2014, and Oct 1, 2017, we enrolled 323 women, of whom 234 had perinatal HIV infection, and reported age at sexual debut and history of heterosexual vaginal intercourse. Of the 172 pregnancies recorded in these women, 147 (85%, 104 livebirths and 43 spontaneous or elective abortions) were eligible for post-pregnancy viral load trajectory analyses (ie, had at least two viral loads in the year after end of pregnancy). Viral load increased by 0·7 log 10 copies per mL (95% CI 0·5 to 1·0) in the first 12 weeks post partum after 104 livebirths, and subsequently stabilised from 13 weeks to 1 year post partum (slope -0·01 log 10 copies per mL, 95% CI -0·3 to 0·3). By comparison, the average viral load trajectory after 43 spontaneous or elective abortions remained at less than 400 copies per mL. We identified three distinct groups of viral load trajectories after 104 livebirths, classified as reflecting sustained suppression (31 [30%]), rebound viraemia (55 [53%]), and persistent viraemia (18 [17%]). Women with sustained post-partum suppression were older at conception (22·9 years, IQR 19·4-25·9) than those with rebound viraemia (20·4 years, 18·8-22·2), or persistent post-partum viraemia (19·0 years, 17·7-20·5). Pre-conception viraemia and immune suppression were also strong risk factors for post-partum viraemia., Interpretation: Despite success achieving viral load suppression during pregnancy, women living with perinatal HIV infection have a high risk of post-partum viraemia. Younger age at conception, pre-conception viraemia, and pre-conception immune suppression could identify women in this population most likely to benefit from post-partum adherence interventions., Funding: National Institutes of Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

With the advent of combined antiretroviral therapies, the face of HIV infection has changed dramatically from a disease with almost certain mortality from serious comorbidities, to a manageable chronic condition with an extended lifespan. In this paper we present the more recent investigations into the epidemiology, microbiology, and pathogenesis of periodontal diseases in patients with HIV, and the effects of combined antiretroviral therapies on the incidence and progression of these diseases both in adults and perinatally infected children. In addition, comparisons and potential interactions between the HIV-associated microbiome, host responses, and pathogenesis in the oral cavity with the gastrointestinal tract and other areas of the body are presented. Also, the effects of HIV and combined antiretroviral therapies on comorbidities such as hyposalivation, dementia, and osteoporosis on periodontal disease progression are discussed., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Lower weight has historically been equated with more severe illness in anorexia nervosa (AN). Reliance on admission weight to guide clinical concern is challenged by the rise in patients with atypical anorexia nervosa (AAN) requiring hospitalization at normal weight., Methods: We examined weight history and illness severity in 12- to 24-year-olds with AN ( n = 66) and AAN ( n = 50) in a randomized clinical trial, the Study of Refeeding to Optimize Inpatient Gains (www.clinicaltrials.gov; NCT02488109). Amount of weight loss was the difference between the highest historical percentage median BMI and admission; rate was the amount divided by duration (months). Unpaired t tests compared AAN and AN; multiple variable regressions examined associations between weight history variables and markers of illness severity at admission. Stepwise regression examined the explanatory value of weight and menstrual history on selected markers., Results: Participants were 16.5 ± 2.6 years old, and 91% were of female sex. Groups did not differ by weight history or admission heart rate (HR). Eating Disorder Examination Questionnaire global scores were higher in AAN (mean 3.80 [SD 1.66] vs mean 3.00 [SD 1.66]; P = .02). Independent of admission weight, lower HR (β = -0.492 [confidence interval (CI) -0.883 to -0.100]; P = .01) was associated with faster loss; lower serum phosphorus was associated with a greater amount (β = -0.005 [CI -0.010 to 0.000]; P = .04) and longer duration (β = -0.011 [CI -0.017 to 0.005]; P = .001). Weight and menstrual history explained 28% of the variance in HR and 36% of the variance in serum phosphorus., Conclusions: Weight history was independently associated with markers of malnutrition in inpatients with restrictive eating disorders across a range of body weights and should be considered when assessing illness severity on hospital admission., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Aim: To examine oral biomarkers that have been associated with periodontal disease progression in HIV-infected adults in perinatally HIV-infected and HIV-exposed but uninfected youth., Material and Methods: This was a cross-sectional, multicentre substudy of youth participating in the Oral Health Pediatric HIV/AIDS Cohort study. Gingival crevicular fluid repository samples from participants with and without periodontal disease (using Gingival Index [GI] and Bleeding on Probing [BOP] parameters on dental examination) were tested for concentration levels of inflammatory biomarkers. Associations were assessed using Wilcoxon test and Spearman correlation., Results: For perinatal HIV youth (n = 129), the markers consistently elevated (p < .05) in sites with GI ≥2 and in sites with BOP were interleukin-1β, 6 and 13, macrophage inflammatory protein-1α and metalloproteinase-9. Serum tumour necrosis factor-α and soluble CD14 were positively correlated with a summary count of elevated cytokines. No associations were seen among HIV-uninfected subjects (n = 71)., Conclusions: The association of oral biomarkers of inflammation with clinical indicators of periodontal inflammation and systemic immune activation suggests that perinatal HIV-infected youth may be at higher risk for developing significant periodontal disease, associated with tooth loss and HIV progression. More frequent dental care of this group is needed to prevent potential periodontal progression., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: Triage tests enhance the efficiency cervical cancer screening based on human papillomavirus (HPV), but the best approach for maximizing programmatic effectiveness is still uncertain, particularly in a real-world scenario., Objective: To compare the clinical performance of 6 triage strategies based on liquid-based cytology (LBC) and HPV-16 and HPV-18 genotyping individually or in combination as sequential triage tests to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher among women with high-risk HPV., Design, Setting, and Participants: This diagnostic study of routine cervical cancer screening was conducted at 100 primary health centers in Tlaxcala, Mexico. Women aged 30 to 64 years were recruited from August 1, 2013, to February 24, 2016, as part of the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage study. Six triage scenarios for referral to colposcopy were examined: (1) LBC testing that found atypical squamous cells of undetermined significance (ASC-US) or worse, (2) positive results in HPV-16 genotyping, (3) positive results in HPV-18 genotyping, (4) positive results in HPV-16/HPV-18 genotyping, (5) positive results in HPV-16 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse, and (6) positive results in HPV-16/HPV-18 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse. Data were analyzed from October 2017 to August 2018., Exposures: Liquid-based cytological testing with simultaneous HPV-16 and HPV-18 genotyping. Women whose HPV genotyping results were positive for HPV-16 or HPV-18 or whose LBC results found ASC-US or worse and a random set of negative and normal results were referred to colposcopy with histologic analysis used for disease confirmation., Main Outcomes and Measures: Clinical performance of each test strategy for detection of CIN grade 2 or higher. Secondary outcomes included resource utilization of each triage scenario, measured by the number of tests performed, the referral rate for colposcopy, and the numbers of colposcopies per CIN grade 2 or higher detected., Results: A total of 36 212 women (median [interquartile range] age, 40 [35-47] years) were screened, and 4051 women (11.2%) had high-risk HPV. Of these women, 1109 (24.6%) were found to have HPV-16, HPV-18, or ASC-US or worse. Further histologic testing detected CIN grade 2 or higher in 110 of 788 women (14.0%) who underwent follow-up colposcopy. Sensitivity and specificity for 3 main triage strategies were 42.9% and 74.0% for LBC; 58.3% and 54.4% for HPV-16/HPV-18 genotyping; and 86.6% and 34.0% for HPV-16/HPV-18 genotyping with reflex LBC. The referral rate to colposcopy was 29% for HPV-16/HPV-18 with reflex LBC, which was 2-fold higher than the referral rate of 12% for LBC., Conclusions and Relevance: Triage of women with high-risk HPV with HPV-16/HPV-18 genotyping with reflex LBC was significantly associated with improvement in detection of CIN grade 2 or higher compared with LBC alone. The benefit of disease prevented may outweigh the cost of increasing requirements for colposcopy services in settings with limited adherence to follow-up after a positive screening result.

Background: Global variation in human papillomavirus (HPV) prevalence and persistence may be explained by differences in risk factors, such as sexual activity, oral contraceptive use, and behavioral factors. We evaluated determinants of acquisition and clearance of HPV infection among young women previously unexposed to HPV., Methods: Five hundred thirty-four women aged 15 to 25 years who were cytology and HPV DNA negative, and seronegative for anti-HPV-16/18 antibodies, were recruited (July 2000-September 2001) from study centers in Brazil, the United States, and Canada (NCT00689741/NCT00120848). They were followed up for 76 months. Cervical samples were HPV genotyped via polymerase chain reaction. We used multivariable (forward stepwise, P = 0.15) Cox proportional hazards regression to estimate rate ratios (RR) and 95% confidence intervals (CI), separately according to length of follow-up time., Results: On short-term follow-up (0-27 months), 257 (48%; 8535.80 person-months; incidence rate = 30.11; 95% CI, 26.64-34.02) incident HPV infections were detected. Marital status, lifetime number of sex partners, history of any sexually transmitted disease, and occasional use of oral contraceptives were strongly associated with acquisition of any HPV. Having 2 or more lifetime sex partners (RR, 2.03; 95% CI, 1.37-3.02) and a history of any sexually transmitted disease (RR, 1.98; 95% CI, 1.19-3.29) were the most important determinants of high-risk HPV (hrHPV) incidence. During the entire follow-up (0-76 months), an increased hrHPV clearance was found among women in North America (RR, 1.38; 95% CI, 1.08-1.78) and black women (RR, 1.64; 95% CI, 1.04-2.60). Greater number of lifetime partners was associated with reduced clearance rates for any HPV (RR, 0.65; 95% CI, 0.43-0.98)., Conclusions: We identified variation in risk of HPV acquisition and clearance among women unexposed to HPV at baseline.

Background: Persons who are infected with human immunodeficiency virus (HIV) are at high risk of human papillomavirus (HPV)-associated cancers. The objectives are to compare antibody titers to HPV 6, 11, 16, and 18 and rate of abnormal cytology between perinatally HIV-infected (PHIV) and perinatally HIV-exposed, uninfected (PHEU) youth., Methods: This is a prospective observational cohort study of HPV4 vaccinated youth performed as part of the multicenter Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Seroconversion and geometric mean titer (GMT) against HPV types 6, 11, 16, and 18 were calculated. Vaccine effectiveness included rates of abnormal cervical cytology and genital warts., Results: Seroconversion to HPV 6, 11, 16, and 18 occurred in 83%, 84%, 90%, and 62% of 310 vaccinated PHIV youth compared to 94%, 96%, 99%, and 87% of 148 vaccinated PHEU youth, respectively (P < .05 for all comparisons). GMTs were lower in the PHIV vs PHEU within each category of HPV4 doses received. Higher GMTs were associated with younger age, lower HIV type 1 RNA viral load, and higher CD4% at first HPV4 vaccination, as well as shorter duration between last vaccine dose and antibody specimen. Abnormal cytology occurred in 33 of 56 PHIV and 1 of 7 PHEU sexually active vaccinated females, yielding incidence rates per 100 person-years of 15.0 (10.9 to 20.6) and 2.9 (0.4 to 22.3), respectively., Conclusion: Antibody titers to HPV4 were lower for all serotypes in PHIV compared to PHEU youth. Protection against abnormal cytology was also diminished in sexually active PHIV females., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer., Methods: We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL., Findings: Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16·5, 95% CI 14·2-19·2, p<0·0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4·4, 3·7-5·3, p<0·0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14·1, 11·1-17·9, p<0·0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical high-risk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12·9, 95% CI 6·7-24·8, p<0·0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2·3, 1·6-3·4, p<0·0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23·1, 9·4-57·0, p<0·0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3·6, 2·5-5·3, p<0·0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women)., Interpretation: HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women., Funding: International Agency for Research on Cancer., (Copyright © 2019 International Agency for Research on Cancer; licensee Elsevier. This is an Open Access article published under the CC BY-NC-ND 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that IARC endorses any specific organisation, products or services. The use of the IARC logo is not permitted. This notice should be preserved along with the article's original URL.)

Executive Summary: The risk of cervical cancer (CC) among women immunosuppressed for a variety of reasons is well documented in the literature. Although there is improved organ function, quality of life and life expectancy gained through use of immunosuppressant therapy, there may be increased long-term risk of cervical neoplasia and cancer and the need for more intense screening, surveillance, and management. Although guidance for CC screening among HIV-infected women (see Table 1) has been supported by evidence from retrospective and prospective studies, recommendations for CC screening among non-HIV immunosuppressed women remains limited because quality evidence is lacking. Moreover, CC screening guidelines for HIV-infected women have changed because better treatments evolved and resulted in longer life expectancy.The objective of this report was to summarize current knowledge of CC, squamous intraepithelial lesions, and human papillomavirus (HPV) infection in non-HIV immunocompromised women to determine best practices for CC surveillance in this population and provide recommendations for screening. We evaluated those with solid organ transplant, hematopoietic stem cell transplant, and a number of autoimmune diseases.A panel of health care professionals involved in CC research and care was assembled to review and discuss existing literature on the subject and come to conclusions about screening based on available evidence and expert opinion. Literature searches were performed using key words such as CC, cervical dysplasia/squamous intraepithelial lesion, HPV, and type of immunosuppression resulting in an initial group of 346 articles. Additional publications were identified from review of citations in these articles. All generated abstracts were reviewed to identify relevant articles. Articles published within 10 years were considered priority for review. Reviews of the literature were summarized with relevant statistical comparisons. Recommendations for screening generated from each group were largely based on expert opinion. Adherence to screening, health benefits and risks, and available clinical expertise were all considered in formulating the recommendations to the degree that information was available., Results: Solid Organ Transplant: Evidence specific for renal, heart/lung, liver, and pancreas transplants show a consistent increase in risk of cervical neoplasia and invasive CC, demonstrating the importance of long-term surveillance and treatment. Reports demonstrate continued risk long after transplantation, emphasizing the need for screening throughout a woman's lifetime.Hematopoietic Stem Cell Transplant: Although there is some evidence for an increase in CC in large cohort studies of these patients, conflicting results may reflect that many patients did not survive long enough to evaluate the incidence of slow-growing or delayed-onset cancers. Furthermore, history of cervical screening or previous hysterectomy was not included in registry study analysis, possibly leading to underestimation of CC incidence rates.Genital or chronic graft versus host disease is associated with an increase in high-grade cervical neoplasia and posttransplant HPV positivity.Inflammatory Bowel Disease: There is no strong evidence to support that inflammatory bowel disease alone increases cervical neoplasia or cancer risk. In contrast, immunosuppressant therapy does seem to increase the risk, although results of observational studies are conflicting regarding which type of immunosuppressant medication increases risk. Moreover, misclassification of cases may underestimate CC risk in this population. Recently published preventive care guidelines for women with inflammatory bowel disease taking immunosuppressive therapy recommend a need for continued long-term CC screening.Systemic Lupus Erythematosus and Rheumatoid Arthritis: The risk of cervical high-grade neoplasia and cancer was higher among women with systemic lupus erythematosus than those with rheumatoid arthritis (RA), although studies were limited by size, inclusion of women with low-grade neoplasia in main outcomes, and variability of disease severity or exposure to immunosuppressants. In studies designed to look specifically at immunosuppressant use, however, there did seem to be an increase in risk, identified mostly in women with RA. Although the strength of the evidence is limited, the increase in risk is consistent across studies.Type 1 DM: There is a paucity of evidence-based reports associating type 1 DM with an increased risk of cervical neoplasia and cancer., Recommendations: The panel proposed that CC screening guidelines for non-HIV immunocompromised women follow either the (1) guidelines for the general population or (2) current center for disease control guidelines for HIV-infected women. The following are the summaries for each group reviewed, and more details are noted in accompanying table:Solid Organ Transplant: The transplant population reflects a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance.Hematopoietic Stem Cell Transplant: These women have a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening. A new diagnosis of genital or chronic graft versus host disease in a woman post-stem cell transplant results in a greater risk of CC than in the general population and should result in more intensive screening and surveillance.Inflammatory Bowel Disease: Women with inflammatory bowel disease being treated with immunosuppressive drugs are at greater risk of cervical neoplasia and cancer than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance. Those women with inflammatory bowel disease not on immunosuppressive therapy are not at an increased risk and should follow screening guidelines for the general population.Systemic Lupus Erythematosus and Rheumatoid Arthritis: All women with systemic lupus erythematosus, whether on immunosuppressant therapy or not and those women with RA on immunosuppressant therapy have a greater risk of cervical neoplasia and cancer than the general population and should follow CC screening guidelines for HIV-infected women. Women with RA not on immunosuppressant therapy should follow CC screening guidelines for the general population.Type 1 Diabetes Mellitus: Because of a lack of evidence of increased risk of cervical neoplasia and cancer among women with type 1 DM, these women should follow the screening guidelines for the general population.

Background: Human papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24 months following a single dose of the nonavalent HPV vaccine among preteen girls and boys., Methods: This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial among 9-11 year-old girls and boys to determine the immunogenicity after a single dose of the nonavalent HPV vaccine (GARDASIL® 9) over 24 months, with a deferred booster dose at 24 months and an optional booster at 30 months after the first dose. Participants provide blood specimens at 6, 12, 18, 24, and 30 months after the first dose. Serologic geometric mean titers (GMT) of the nine vaccine types (HPV 16/18/ 6/11/31/33/45/52/58) will be measured at each time point. The primary objective is to determine the stability of type-specific serologic GMT of HPV16 and HPV18 between the 6- vs. 12-month, 12- vs. 18-month, and 18- vs. 24-month visits. Secondary objectives are to determine the stability of type-specific serologic GMT of the other HPV types (HPV 6/11/31/33/45/52/58) between the visits and to assess safety and reactogenicity after each vaccine dose., Discussion: Single dose HPV vaccination could simplify the logistics and reduce costs of HPV vaccination in the US and across the world. This study will contribute important immunogenicity data on the stability and kinetics of type-specific antibody titers and inform feasibility of the single dose HPV vaccination paradigm., Trial Registration: ClinicalTrials.gov Identifier: NCT02568566 . Registered on October 6, 2015.

Toll-like receptors (TLRs) are innate immune defenders thought to be critical for the clearance of human papillomavirus (HPV) infections hence preventing the development of HPV-associated high-grade cervical intra-epithelial neoplasia (CIN2 or 3), a potential cervical cancer precursor. However, the role of TLRs in the regression of established cervical lesions, such as CIN2, is hindered by a lack of prospective design studies. Using SYBR green real-time PCR assays, we have examined the gene expression of TLR2, TLR3, TLR7, TLR8 and TLR9, in cytobrush collected endocervical cells of 63 women diagnosed with CIN2 at study entry (baseline) and followed over a 3-year period. Wilcoxon rank-sum test was used to examine the association between TLR expression levels, measured at baseline, and CIN2 outcome (regression vs. persistence/progression) over time. HPV genotyping was performed using Roche Linear Array Assay detecting 37 HPV types. Women with CIN2 regression showed significantly higher baseline levels of TLR2 (p = 0.006) and TLR7 (p = 0.007), as well as a non-significant trend for a higher TLR8 expression (p = 0.053) compared to women with CIN2 persistence/progression. Six women with CIN2 regression, who presented with an HR-HPV DNA-negative CIN2 lesion at study entry, had significantly higher baseline levels of TLR2 (p = 0.005), TLR7 (p = 0.013) and TLR8 (p = 0.012), compared to women with CIN2 persistence/progression, suggesting their role in clearance of HPV prior to clearance of the lesion. Our results confirm a key role of TLRs in regression of CIN2 and support the potential use of TLR-agonists for treatment of these lesions., (© 2018 UICC.)

Objectives: This study explores the association between combination antiretroviral therapy (cART) and oral health outcomes (dental and periodontal) among perinatally HIV-infected (PHIV) youth., Methods: We conducted a cross-sectional study of oral health among PHIV youth participating in the Oral Health substudy of the Pediatric HIV/AIDS Cohort Study (PHACS). Dentists at research sites were trained/calibrated on how to perform a standardized oral mucosal, dental and periodontal examination. They assessed the decayed-missing-filled-surfaces and teeth index (DMFS/T). The number of decayed surfaces and teeth and the number of teeth with gingival bleeding on probing for each participant were derived from the examination. Data for analysis included lifetime measurements of CD4 cell count and viral load, sociodemographic information and current/past history of ART., Results: Among 209 PHIV youth, 95% were on ART at the time of enrolment. Among 143 PHIV youth on the same cART for at least 1 year, we found that the mean decayed teeth score of those receiving cART containing an integrase inhibitor was 86% higher than that of those on cART without an integrase inhibitor after adjusting for age, lifetime proportion of unsuppressed viral load and CD4 cell count nadir. Initiating protease inhibitors before age 6 years was associated with a significantly lower DMFT score than participants who initiated at age 6 years and older., Conclusion: Our study revealed that PHIV youth who received cART containing an integrase inhibitor had a significantly higher number of untreated active caries than those on cART without an integrase inhibitor. This may warrant closer dental surveillance of those receiving an integrase inhibitor.

Objective: Guidelines recommend 3-year cervical cancer screening intervals to avoid unnecessary invasive procedures; however, regular testing remains critical. We evaluated trends in cervical cancer screening among low-income women receiving family planning-related services and their association with patient and provider characteristics., Materials and Methods: Using claims and enrollment data from California's publicly funded family planning program, we identified 540,026 women with a clinician visit at 216 sites between 2011 and 2015. We calculated guideline adherent cervical cancer testing rates for 6-month periods among women aged 21 to 24, 25 to 29, and 30 to 64 years. We also calculated guideline adherent chlamydia testing for women aged 21 to 24 years., Results: Having a 3-year cervical cancer screening test declined for all age groups. The odds of cervical cancer screening declined for women aged 21 to 24 years by an estimated 11% every 6 months (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.89-0.90), a significantly greater decline than for the other age groups. Among women aged 21 to 29 years, the decrease was significantly larger for Latina (ratio of ORs = 0.95, 95% CI = 0.95-0.96) and Spanish-speaking (ratio of ORs = 0.95, 95% CI = 0.95-0.96) women compared with non-Latina and non-Spanish-speaking women. A smaller decline was seen for chlamydia screening., Conclusions: Changes in screening interval guidelines are associated with overall decreased screening. This trend was strongest among women aged 21 to 24 years, even as they continued to be screened appropriately for chlamydia, suggesting many missed opportunities. Efforts to reduce unnecessary cervical cancer screening should be monitored to maintain appropriate screening rates to avoid advanced-stage diagnoses and higher health care costs.

Human Papillomavirus (HPV) is the most common sexually transmitted infection in the USA, with over 14 million people acquiring HPV each year. HPV is also the cause of most anogenital cancers. About 90% of HPV infections spontaneously resolve over 3 years. However, about 10% remain as persistent infection defined as repeatedly detected in cervical samples. As HPV is controlled by local and systemic immune responses, individuals with immunosuppression are at risk for cervical cancer. It is hypothesized that immunosuppressed individuals are more likely to have HPV persistence, which is necessary for malignant transformation. Accordingly, women with rheumatic diseases such as SLE and RA are likely vulnerable to HPV infection and the progression of cervical disease. The HPV vaccine, given as a series of vaccinations, is safe and effective that can prevent HPV infection and cervical cancer. There is no contraindication to HPV vaccination for women to age 26 with rheumatic disease, as it is not live. As in the general population, timing is key for the efficacy of the HPV vaccine as the goal is to vaccinate prior to sexual debut and exposure to HPV. There are no formal recommendations for cervical cancer screening in women with rheumatic disease but recommendations for the HIV-positive population can be adopted, meaning to screen with a Pap test annually for three consecutive years and if all normal, to extend the interval to every 3 years with the option of co-testing with HPV at 30 years and older.

Background: Microbially mediated oral diseases can signal underlying HIV/AIDS progression in HIV-infected adults. The role of the oral microbiota in HIV-infected youth is not known. The Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study is a longitudinal study of perinatally HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) youth. We compared oral microbiome levels and associations with caries or periodontitis in 154 PHIV and 100 PHEU youth., Results: Species richness and alpha diversity differed little between PHIV and PHEU youth. Group differences in average counts met the significance threshold for six taxa; two Corynebacterium species were lower in PHIV and met thresholds for noteworthiness. Several known periodontitis-associated organisms (Prevotella nigrescens, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Filifactor alocis) exhibited expected associations with periodontitis in PHEU youth, associations not observed in PHIV youth. In both groups, odds of caries increased with counts of taxa in four genera, Streptococcus, Scardovia, Bifidobacterium, and Lactobacillus., Conclusions: The microbiomes of PHIV and PHEU youth were similar, although PHIV youth seemed to have fewer "health"-associated taxa such as Corynebacterium species. These results are consistent with the hypothesis that HIV infection, or its treatment, may contribute to oral dysbiosis.

Objective: To determine the magnitude and persistence of quadrivalent human papillomavirus (HPV)16 and HPV18 B-cell and T-cell memory after three or four doses of quadrivalent HPV vaccine (QHPV) in HIV-infected children., Methods: Seventy-four HIV-infected children immunized with four doses and 23 with three doses of QHPV had HPV16 and HPV18 IgG B-cell and IFNγ and IL2 T-cell ELISPOT performed at 2, 3.5 and 4-5 years after the last dose., Results: HPV16 and HPV18 T-cell responses were similar in both treatment groups, with higher responses to HPV16 vs. HPV18. These HPV T-cell responses correlated with HIV disease characteristics at the study visits. Global T-cell function declined over time as measured by nonspecific mitogenic stimulation. B-cell memory was similar across treatment groups and HPV genotypes. There was a decline in HPV-specific B-cell memory over time that reached statistical significance for HPV16 in the four-dose group., Conclusion: B-cell and T-cell memory did not significantly differ after either three or four doses of QHPV in HIV-infected children. The clinical consequences of decreasing global T-cell function and HPV B-cell memory over time in HIV-infected children requires further investigation.

Objectives: The American Society for Colposcopy and Cervical Pathology Colposcopy Standards address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. Working Group 1 was tasked with defining the role of colposcopy, describing benefits and potential harms, and developing an official terminology., Methods: A systematic literature review was performed. A national survey of American Society for Colposcopy and Cervical Pathology members provided input on current terminology use. The 2011 International Federation for Cervical Pathology and Colposcopy terminology was used as a template and modified to fit colposcopic practice in the United States. For areas without data, expert consensus guided the recommendation. Draft recommendations were posted online for public comment and presented at an open session of the 2017 International Federation for Cervical Pathology and Colposcopy World Congress for further comment. All comments were considered for the final version., Results: Colposcopy is used in the evaluation of abnormal or inconclusive cervical cancer screening tests. Colposcopy aids the identification of cervical precancers that can be treated, and it allows for conservative management of abnormalities unlikely to progress. The potential harms of colposcopy include pain, psychological distress, and adverse effects of the procedure. A comprehensive colposcopy examination should include documentation of cervix visibility, squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), lesion(s) visibility, size and location of lesions, vascular changes, other features of lesion(s), and colposcopic impression. Minimum criteria for reporting include squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), and colposcopic impression., Conclusions: A recommended terminology for use in US colposcopic practice was developed, with comprehensive and minimal criteria for reporting.