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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.

BackgroundUnderstanding 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.MethodsWe 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.ResultsHuman 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.ConclusionsThis 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.

BackgroundAge-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention.MethodsWe 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.ResultsIn 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+.ConclusionsAge-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.

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.

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.

PurposeCurrent 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.MethodsThis 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.ResultsCompared 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

IntroductionThis 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.MethodsThe 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.ResultsThe 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.ConclusionsProviding 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 registrationThis study is registered at www.clinicaltrials.gov NCT02270021.

Background and objectivesWe 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.MethodsIn 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.ResultsOf 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.ConclusionsThe 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.

IntroductionSalivary 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.ObjectiveAs 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.MethodsWe 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.ResultsWe 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.ConclusionThe 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.

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.

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.

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.

AimTo 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 methodsThis 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.ResultsFor perinatal HIV youth (n = 129), the markers consistently elevated (p

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.

ObjectivesThis study explores the association between combination antiretroviral therapy (cART) and oral health outcomes (dental and periodontal) among perinatally HIV-infected (PHIV) youth.MethodsWe 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.ResultsAmong 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.ConclusionOur 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.

ObjectiveGuidelines 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 methodsUsing 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.ResultsHaving 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.ConclusionsChanges 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.

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.

ObjectivesThe 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.MethodsA 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.ResultsColposcopy 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.ConclusionsA recommended terminology for use in US colposcopic practice was developed, with comprehensive and minimal criteria for reporting.

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of colposcopy and directed biopsy for cervical cancer prevention in the United States (US). The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. An extensive literature review was conducted and supplemented by a systematic review and meta-analysis of unpublished data. In addition, a survey of practicing colposcopists was conducted to assess current colposcopy practice in the US. Recommendations were approved by the working group members, and the final revisions were made based on comments received from the public. The recommendations cover terminology, risk-based colposcopy, colposcopy procedures, and colposcopy adjuncts. The ASCCP Colposcopy Standards recommendations are an important step toward raising the standard of colposcopy services delivered to women in the US. Because cervical cancer screening programs are currently undergoing important changes that may affect colposcopy performance, updates to some of the current recommendations may be necessary in the future.

ObjectivesThe 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.MethodsA 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.ResultsColposcopy 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.ConclusionsA recommended terminology for use in US colposcopic practice was developed, with comprehensive and minimal criteria for reporting.

Persistent infection with oncogenic human papillomavirus (HPV) is necessary but not sufficient for the development of cervical cancer. The factors promoting persistence as well those triggering carcinogenetic pathways are incompletely understood. Rapidly evolving evidence indicates that the vaginal microbiome (VM) may play a functional role (both protective and harmful) in the acquisition and persistence of HPV, and subsequent development of cervical cancer. The first studies examining the VM and the presence of an HPV infection using next-generation sequencing techniques identified higher microbial diversity in HPV-positive as opposed to HPV-negative women. Furthermore, there appears to be a temporal relationship between the VM and HPV infection in that specific community state types may be correlated with a higher chance of progression or regression of the infection. Studies describing the VM in women with preinvasive disease (squamous intraepithelial neoplasia [SIL]) consistently demonstrate a dysbiosis in women with the more severe disease. Although it is plausible that the composition of the VM may influence the host's innate immune response, susceptibility to infection, and the development of cervical disease, the studies to date do not prove causality. Future studies should explore the causal link between the VM and the clinical outcome in longitudinal samples from existing biobanks.

AimsTo compare the prevalence and severity of periodontal diseases between 180 perinatally HIV-infected (PHIV) and 118 perinatally HIV-exposed and uninfected (PHEU) youth in a cross-sectional study conducted at 11 clinical sites in the United States and Puerto Rico from the Adolescent Master Protocol study of the Pediatric HIV/AIDS cohort study (PHACS) network.MethodsSeveral analyses were conducted, employing the current CDC/AAP classification for periodontitis and incorporating a definition of gingivitis based on a bleeding on probing (BOP) threshold, and analyses based on more detailed whole-mouth, intra-oral regionally, site-based and tooth-based criteria of BOP, plaque levels, pockets depths and clinical attachment levels.ResultsAfter adjusting for plaque control habits and behavioural and sociodemographic factors, there were no significant differences in periodontal diseases between the PHIV and PHEU youth using any of these criteria. For PHIV youth, there was no significant association between parameters of periodontal disease and current HIV status.ConclusionsAlthough no significant differences in periodontal parameters were noted between the PHIV and PHEU youth, the influence of antiretroviral therapy merits further exploration in this cohort in a longitudinal study.

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. [ABSTRACT FROM AUTHOR]

In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV-infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV.

ObjectiveTo compare oral health parameters in perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected youth (PHEU).MethodsIn a cross-sectional substudy within the Pediatric HIV/AIDS Cohort Study, participants were examined for number of decayed teeth (DT), Decayed, Missing, and Filled Teeth (DMFT), oral mucosal disease, and periodontal disease (PD). Covariates for oral health parameters were examined using zero-inflated negative binomial regression and ordinal logistic regression models.ResultsEleven sites enrolled 209 PHIV and 126 PHEU. Higher DT scores were observed in participants who were PHIV [Adjusted Mean Ratio (aMR) = 1.7 (95% CI 1.2-2.5)], female [aMR = 1.4 (1.0-1.9)], had no source of regular dental care [aMR = 2.3 (1.5-3.4)], and had a high frequency of meals/snacks [≥5 /day vs 0-3, aMR = 1.9 (1.1-3.1)] and juice/soda [≥5 /day vs 0-3, aMR = 1.6 (1.1-2.4)]. Higher DMFT scores were observed in participants who were older [≥19, aMR = 1.9 (1.2-2.9)], had biological parent as caregiver [aMR = 1.2 (1.0-1.3)], had a high frequency of juice/soda [≥5 /day vs 0-3, aMR = 1.4 (1.1-1.7)] and a low saliva flow rate [mL/min, aMR = 0.8 per unit higher (0.6-1.0)]. Eighty percent had PD; no differences were seen by HIV status using the patient-based classifications of health, gingivitis or mild, moderate, or severe periodontitis. No associations were observed of CD4 count and viral load with oral health outcomes after adjustment.ConclusionsOral health was poor in PHIV and PHEU youth. This was dismaying since most HIV infected children in the U.S. are carefully followed at medical health care clinics. This data underscore the need for regular dental care. As PHIV youth were at higher risk for cavities, it will be important to better understand this relationship in order to develop targeted interventions.

ObjectiveThe incidence of anal cancer is higher in women than men in the general population and has been increasing for several decades. Similar to cervical cancer, most anal cancers are associated with human papillomavirus (HPV), and it is believed that anal cancers are preceded by anal high-grade squamous intraepithelial lesions (HSIL). Our goals were to summarize the literature on anal cancer, HSIL, and HPV infection in women and to provide screening recommendations in women.MethodsA group of experts convened by the American Society for Colposcopy and Cervical Pathology and the International Anal Neoplasia Society reviewed the literature on anal HPV infection, anal SIL, and anal cancer in women.ResultsAnal HPV infection is common in women but is relatively transient in most. The risk of anal HSIL and cancer varies considerably by risk group, with human immunodeficiency virus-infected women and those with a history of lower genital tract neoplasia at highest risk compared with the general population.ConclusionsWhile there are no data yet to demonstrate that identification and treatment of anal HSIL leads to reduced risk of anal cancer, women in groups at the highest risk should be queried for anal cancer symptoms and required to have digital anorectal examinations to detect anal cancers. Human immunodeficiency virus-infected women and women with lower genital tract neoplasia may be considered for screening with anal cytology with triage to treatment if HSIL is diagnosed. Healthy women with no known risk factors or anal cancer symptoms do not need to be routinely screened for anal cancer or anal HSIL.

Human papillomavirus (HPV) genotype 52 is commonly found in Asian cases of cervical cancer but is rare elsewhere. Analysis of 611 isolates collected worldwide revealed a remarkable geographical distribution, with lineage B predominating in Asia (89.0% vs 0%-5.5%; P(corrected) < .001), whereas lineage A predominated in Africa, the Americas, and Europe. We propose that the name "Asian lineage" be used to denote lineage B, to signify this feature. Preliminary analysis suggested a higher disease risk for lineage B, although ethnogeographical confounders could not be excluded. Further studies are warranted to verify whether the reported high attribution of disease to HPV52 in Asia is due to the high prevalence of lineage B.

BackgroundAnal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women.MethodsYoung women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models.ResultsSeventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P < .001), weekly alcohol use (P = .015), anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence.ConclusionsThe majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence.

Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph 'Comprehensive Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters.

PurposeCurrent recommendations for refeeding in anorexia nervosa (AN) are conservative, beginning around 1,200 calories to avoid refeeding syndrome. We previously showed poor weight gain and long hospital stay using this approach and hypothesized that a higher calorie approach would improve outcomes.MethodsAdolescents hospitalized for malnutrition due to AN were included in this quasi-experimental study comparing lower and higher calories during refeeding. Participants enrolled between 2002 and 2012; higher calories were prescribed starting around 2008. Daily prospective measures included weight, heart rate, temperature, hydration markers and serum phosphorus. Participants received formula only to replace refused food. Percent Median Body Mass Index (%MBMI) was calculated using 50th percentile body mass index for age and sex. Unpaired t-tests compared two groups split at 1,200 calories.ResultsFifty-six adolescents with mean (±SEM) age 16.2 (±.3) years and admit %MBMI 79.2% (±1.5%) were hospitalized for 14.9 (±.9) days. The only significant difference between groups (N = 28 each) at baseline was starting calories (1,764 [±60] vs. 1,093 [±28], p < .001). Participants on higher calories had faster weight gain (.46 [±.04] vs. .26 [±.03] %MBMI/day, p < .001), greater daily calorie advances (122 [±8] vs. 98 [±6], p = .024), shorter hospital stay (11.9 [±1.0] vs. 17.6 [±1.2] days, p < .001), and a greater tendency to receive phosphate supplementation (12 vs. 8 participants, p = .273).ConclusionsHigher calorie diets produced faster weight gain in hospitalized adolescents with AN as compared with the currently recommended lower calorie diets. No cases of the refeeding syndrome were seen using phosphate supplementation. These findings lend further support to the move toward more aggressive refeeding in AN.