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Introduction Demonstrating human papillomavirus vaccine impact is critical for informing guidelines to increase vaccination and decrease human papillomavirus‒related outcomes, particularly in states with suboptimal vaccination coverage, such as Tennessee. This study examines the trends in high-grade cervical lesion incidence among Tennessee Medicaid-enrolled women aged 18–39 years and the subset of women who were screened for cervical cancer. Methods Using a validated claims-based model to identify incident cervical intraepithelial neoplasia Grades 2 or 3 or adenocarcinoma in situ events, annual age group‒specific incidence rates from Tennessee Medicaid billing data, 2008–2018, were calculated. Significant trends were determined by Joinpoint. Analyses were conducted in 2020. Results From 2008 to 2018, high-grade cervical lesion incidence significantly declined in women aged 18–20 years (average annual percentage change= −31.9, 95% CI= −38.6, −24.6), 21–24 years (average annual percentage change= −12.9, 95% CI= −22.3, −2.4), and 25–29 years (average annual percentage change= −6.4, 95% CI= −8.1, −4.6). Among screened women, rates significantly declined for ages 18–20 years (average annual percentage change= −20.3, 95% CI= −25.3, −15.0), 21–24 years (average annual percentage change= −10.2, 95% CI= −12.6, −7.8), and 25–29 years (average annual percentage change= −2.6, 95% CI= −3.9, −1.2). Trends from 2008 to 2018 were stable for older age groups (30–34 and 35–39 years). Conclusions Results show reductions in high-grade cervical lesion incidence among ages most likely to have benefited from the human papillomavirus vaccine. Declines among young, screened women suggest causes other than reduction in screening. Evidence of vaccine impact in populations with low-vaccination coverage, such as Tennessee, is promising.

Background Little is known about the role of early obesity or weight change during adulthood in the development of liver cancer and biliary tract cancer (BTC). Methods We investigated the associations of body mass index (BMI) and weight trajectories with the risk of liver cancer and BTC in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. BMI was self-reported at ages 20 years and 50 years and at enrollment. BMI trajectories were determined using latent class growth models. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a median follow-up of 15.9 years among 138 922 participants, 170 liver cancer and 143 BTC cases were identified. Compared with those whose BMI did not exceed 25 kg/m2, participants with BMI exceeding 25 kg/m2 at age 20 years had increased risks of liver cancer (HR = 2.03, 95% CI = 1.26 to 3.28) and BTC (HR = 1.99, 95% CI = 1.16 to 3.39). Compared with participants maintaining normal BMI until enrollment, trajectory of normal weight at age 20 years to obesity at enrollment was associated with increased risk for liver cancer (HR = 2.50, 95% CI = 1.55 to 4.04) and BTC (HR = 1.83, 95% CI = 1.03 to 3.22). Compared with adults with stable weight (±5 kg) between age 20 years and 50 years, weight gain of 20 kg and greater between ages 20 years and 50 years had higher hazard ratios of 2.24 (95% CI = 1.40 to 3.58) for liver cancer and 1.86 (95% CI = 1.12 to 3.09) for BTC. Conclusions Being overweight and/or obese at age 20 years and BMI trajectories that result in being overweight and/or obese may increase risk for both liver cancer and BTC.

Background Anal cancer is rare in the general population in both genders in the US, but an increased incidence of anal cáncer (AC) has been reported among people living with HIV-1 infection (PLWH) and little is known among the population in South US. Methods In a retrospective study design, electronic health records from 2006 to 2018 were reviewed in a HIV clinical cohort at the University of Alabama at Birmingham. Associations of demographic, sociodemographic, and HIV-clinical indicators were examined in univariate analyses between high-grade squamous intraepithelial lesions (HSIL) and AC cases and condition-free individuals. Factors for anal/rectal cytology screening tests among PLWH were also assessed over time. Ages at onset of anal cancer were compared with the general US population reported by the National Surveillance, Epidemiology, and End Results Program. Results A total of 79 anal HSIL (96% men) and 43 cancer (100% men) patients were observed along with 4367 HSIL/cancer-free patients (75.9% men). HSIL (P P Conclusion AC incidence among HIV-infected men was 161 times higher than general population with an earlier age of onset/diagnosis. Many patients with AC had missed screening opportunities that could potentially have captured neoplasia in pre-cancerous stages. AC-related screening guidelines need to be integrated into routine clinical care, especially among PLWH at highest risk such as MSM and those with lower CD4 counts.

Background:Previous studies show an association between smoking and anal cancer. The objective of this study was to assess the association between smoking and anal HPV (human papillomavirus) prevalence, incidence, and persistence in men.Methods:The HPV Infection in Men (HIM) Study is a multinational study that enrolled HIV-negative men. At baseline and follow-up visits, anal specimens were collected. HPV genotyping was assessed by linear array. Prevalence ratios (PR) were used to assess the association between smoking and anal HPV prevalence. Odds ratios (OR) were used to assess the association between smoking and anal HPV incidence and ≥12-months persistence.Results:Current smokers have a higher prevalence [adjusted PR (aPR), 1.36; 95% confidence interval (CI), 1.06–1.73) and incidence [adjusted OR (aOR), 1.74; 95% CI, 1.26–2.39] and ≥12-months persistence (aOR, 1.67; 95% CI, 1.19–2.33) of any anal HPV compared with never smokers. There were no differences in the prevalence, incidence, or persistence of anal HPV between former and never smokers. Smoking status was not associated with the prevalence or persistence of anal HPV among men who have sex with men but was associated with higher incidence of HR-HPV. Among men that have sex with women (MSW), current smokers had an increased prevalence and incidence of LR-HPV compared with never smokers.Conclusions:Current smokers had a higher prevalence, persistence, and incidence of HPV compared with never smokers. Further research is needed to assess the role smoking in anal HPV persistence and progression to disease.Impact:Prevention initiatives should raise awareness about smoking and the risk factor of anal HPV infection and anal cancer.

BackgroundIndependent of CD4 cell count, low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the USA and Canada.MethodsWe examined all cancer-free PWH with one or more CD4/CD8 values from NA-ACCORD observational cohorts with validated cancer diagnoses between 1998-2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines.Models were adjusted for age, sex, race/ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.ResultsAmong 83,893 PWH, there were 5,628 incident cancers, including lung cancer (n=755), Kaposi sarcoma (KS, n=501), non-Hodgkin lymphoma (NHL, n=497), and anal cancer (n=439). Median age at cohort entry was 43 years, 87% were male, and 43% were white. Overall median six-month lagged CD4/CD8 ratio was 0.52 (interquartile range: 0.30-0.82). Compared with six-month lagged CD4/CD8=0.80, CD4/CD8=0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval: 1.14-1.35]). CD4/CD8 ratio was also inversely associated with NHL, KS, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all pConclusionsLow CD4/CD8 ratio up to 24 months prior to cancer diagnosis was independently associated with increased cancer risk in PWH and may serve as a clinical biomarker.

Objectives While most human papillomavirus (HPV) infection clears on its own, persistent HPV infection can cause genital warts and anal, penile and oropharyngeal cancers in men. We conducted genetic analysis in a sub-cohort of the HPV infection in men (HIM) study to test the hypothesis that differences in host genes influence HPV persistence in men. Methods Baseline and longitudinal genital HPV status at the genitals was measured every 6-months using the Linear Array assay amplified HPV L1 gene fragment using the PGMY09/11 L1 consensus primer system. DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) in the customized genome-wide genotyping array, the “TxArray,” were examined using logistic regression in a case-control study design to assess the association with HPV16 persistence/clearance. Results Of the total of 737,742 autosomal SNPs in the array, 605,885 passed basic quality control and were examined between 40 men (cases) with > 18 months persistent genital HPV 16 infection vs. 151 controls who were HPV 16-positive, but whose infections cleared in, Highlights • HPV persist in anogenital area of some men but not in others. • Several genomic variants indicate association with HPV 16 persistence in men. • Extreme phenotype, HPV persistence that occurs in 10-15% of HPV infected individuals in our study, have power to detect associations, even with small samplesize. • This is the first genetic study related to persistent HPV 16 infection in men and has tremendous potential to identify biomarkers.

Objective Young women in South Africa are highly affected by sexually transmitted infections (STI), like C. trachomatis (CT) and N. gonorrhoeae (NG). We aimed to estimate the incidence of CT and NG, and its determinants, among young women from the Western Cape, South Africa, participating in an HPV vaccine trial (the EVRI study). Methods HIV-negative women aged 16–24 years were enrolled between October 2012 and July 2013. At enrolment and month 6 participants were screened for CT and NG (Anyplex CT/NG real-time detection method). A questionnaire on demographic and sexual history characteristics was completed at enrolment and month 7. Treatment for CT and/or NG was offered to infected participants. Incidence rates (IR) of CT and NG were estimated. Determinants of incident CT and NG infections were assessed using Poisson regression. Results 365 women were tested for CT and/or NG at least twice. Prevalence of CT and NG at baseline was 33.7% and 10.4%, respectively. Prevalence of co-infection with CT and NG was 7.1%. During 113.3 person-years (py), 48 incident CT infections were diagnosed (IR = 42.4 per 100 py, 95% confidence interval (CI) 31.9–56.2). Twenty-nine incident NG were diagnosed during 139.3 py (IR = 20.8 per 100 py, 95%CI 14.5–29.9). Prevalent CT infection at baseline was associated with incident CT (adjusted incidence rate ratio (aIRR) 5.8, 95%CI 3.0–11.23. More than three lifetime sex partners increased the risk for incident NG (3–4 partners aIRR = 7.3, 95%CI 2.1–26.0; ≥5 partners aIRR = 4.3, 95%CI 1.1–17.5). Conclusions The IR of bacterial STIs among young women in the Western Cape is very high. Besides being previously infected and a higher lifetime number of sex partners, no other risk factors were found for CT and NG, suggesting that the majority of these women were at risk. This indicates the need for intensified prevention of STIs as well as screening and treatment programs to increase sexual health in this region.

BackgroundLiver cancer incidence in the United States is higher among African Americans compared to Whites. The purpose of this study was to examine differences in risk factors associated with Hepatocellular carcinoma (HCC) among Whites and African Americans from low socioeconomic backgrounds in the Southern Community Cohort Study (SCCS).MethodsThe SCCS is a prospective cohort study with participants from the southeastern US. HCC incidence rates were calculated. Multivariable Cox regression was used to calculate HCC adjusted hazard ratios (aHR) associated with known baseline HCC risk factors for Whites and African Americans, separately.ResultsThere were 294 incident HCC. The incidence rate ratio for HCCwas higher (IRR=1.4, 95%CI: 1.1-1.9) in African Americans compared to Whites. Whites saw a stronger association between self-reported Hepatitis C Virus (aHR= 19.24, 95%CI: 10.58-35.00) and diabetes (aHR= 3.55, 95%CI: 1.96-6.43) for the development of HCCcompared to African Americans (aHR= 7.73, 95%CI: 5.71-10.47 and aHR = 1.48, 95%CI: 1.06-2.06, respectively) even though the prevalence of these risk factors was similar between races. Smoking (aHR= 2.91, 95%CI: 1.87-4.52) and heavy alcohol consumption (aHR= 1.59, 95%CI: 1.19-2.11) were significantly associated with HCC risk among African Americans only.ConclusionsIn this large prospective cohort, we observed racial differences in HCC incidence and risk factors associated with HCC among African Americans and Whites.ImpactUnderstanding HCC risk differences can assist prevention strategies that target people at high risk, potentially based on risk factors that differ by race.

Background Both diabetes and liver cancer are overrepresented among African Americans, but limited information is available on the interrelationship of these two diseases among African Americans. We examined the association of diabetes with the incidence of liver cancer and whether this varied by participant self-reported race/ethnicity. Methods Using the Southern Community Cohort Study, we conducted a cancer follow up (2002–2016) of a cohort of mostly low-income participants aged 40–79 with diabetes (n = 15,879) and without diabetes (n = 59,077) at study baseline. Cox regression was used to compute Hazard Ratios (HR) and 95% CIs for the risk of incident liver cancer. Results With 790,132 person years of follow up, 320 incident cases of liver cancer were identified. In analyses controlling for age, sex, race, BMI, current and former smoking, total alcohol consumption, family history of liver cancer, any hepatitis infection, hyperlipidemia and socioeconomic factors, the association between diabetes and risk of liver cancer differed significantly (pinteraction = 0.0001) between participants identifying as Black/African American (AA) or White/European American (EA). Diabetes was associated with 5.3-fold increased cancer risk among EAs (HR 5.4, 95% CI 3.2–9.3) vs an 80% increase (HR 1.8, 95% CI 1.3–2.5) among AAs. Furthermore, controlling for diabetes greatly attenuated the higher risk of liver cancer among AAs; indeed, while the cancer risk among those without diabetes was twice as high among AAs than EAs (HR = 2.0, 95% CI = 1.4–2.9), no excess in AAs was observed among those with diabetes (HR = 0.7, 95% CI = 0.4–1.1). Conclusion While liver cancer risk in general is greater in AAs than EAs and diabetes increases this risk in both racial/ethnic groups, diabetes appears to impact liver cancer to a much greater extent among EAs. The findings raise the possibility of racially different mechanisms and impacts of diabetes on this often fatal cancer among AAs and EAs.

Background The purpose of this study was to assess genital recurrence of human papillomavirus (HPV) genotypes included in the 9-valent vaccine and to investigate factors associated with recurrence among men in the HPV Infection in Men (HIM) Study. Methods Men were followed every 6 months for a median of 3.7 years. HPV genotypes were detected using Roche linear array. Factors associated with type-specific HPV recurrence (infections occurring after a ≥12-month infection-free period) were assessed. Results In type-specific analyses, 31% of prior prevalent and 20% of prior incident infections recurred. Among prevalent infections, HPV types 52, 45, 16, 58, and 6 and among incident infections, HPV types 58, 52, 18, 16, and 11 had the highest rates of recurrence. New sexual partners (male or female) and frequency of sexual intercourse with female partners were associated with HPV-6, -16, -31, and -58 infection recurrence. In grouped analyses, lifetime and new male sexual partners were associated with recurrence of prior incident infection with any of the 9 HPV types. Conclusions Recurrence of genital HPV infections is relatively common among men and associated with high-risk sexual behavior. Further studies are needed to understand the role of HPV recurrence in the etiology of HPV-associated diseases.

Disparities in human papillomavirus (HPV) vaccination exist between urban (metropolitan statistical areas (MSAs)) and rural (non-MSAs) regions. To address whether the HPV vaccine’s impact differs by urbanicity, we examined trends in cervical intraepithelial neoplasia grades 2 or 3 and adenocarcinoma in situ (collectively, CIN2+) incidence in MSAs and non-MSAs among Tennessee Medicaid (TennCare)-enrolled women aged 18–39 years and among the subset screened for cervical cancer in Tennessee, United States. Using TennCare claims data, we identified annual age-group-specific (18–20, 21–24, 25–29, 30–34, and 35–39 years) CIN2+ incidence (2008–2018). Joinpoint regression was used to identify trends over time. Age–period–cohort Poisson regression models were used to evaluate age, period, and cohort effects. All analyses were stratified by urbanicity (MSA versus non-MSA). From 2008–2018, 11,243 incident CIN2+ events (7956 in MSAs, 3287 in non-MSAs) were identified among TennCare-enrolled women aged 18–39 years. CIN2+ incident trends (2008–2018) were similar between women in MSAs and non-MSAs, with largest declines among ages 18–20 (MSA average annual percent change (AAPC): −30.4, 95% confidence interval (95%CI): −35.4, −25.0, non-MSA AAPC: −30.9, 95%CI: −36.8, −24.5) and 21–24 years (MSA AAPC: −14.8, 95%CI: −18.1, −11.3, non-MSA AAPC: −15.1, 95%CI: −17.9, −12.2). Significant declines for ages 18–20 years began in 2008 in MSAs compared to 2010 in non-MSAs. Trends were largely driven by age and cohort effects. These patterns were consistent among screened women. Despite evidence of HPV vaccine impact on reducing CIN2+ incidence regardless of urbanicity, significant declines in CIN2+ incidence were delayed in non-MSAs versus MSAs.

Simple Summary Liver cancer incidence in the United States is higher among African Americans compared to White Americans. The determinants of racial disparities in liver cancer incidence are not clear. Using data from White and African Americans from low socioeconomic backgrounds, we compared the prevalence of known liver cancer risk factors by race and assessed factors associated with liver cancer incidence. Understanding liver cancer risk differences can assist prevention strategies that target people at high risk, potentially based on risk factors that differ by race. Abstract The purpose of this study was to examine differences in risk factors associated with hepatocellular carcinoma (HCC) among White and African Americans from low socioeconomic backgrounds in the Southern Community Cohort Study (SCCS). The SCCS is a prospective cohort study with participants from the southeastern US. HCC incidence rates were calculated. Multivariable Cox regression was used to calculate HCC-adjusted hazard ratios (aHR) associated with known baseline HCC risk factors for White and African Americans, separately. There were 294 incident HCC. The incidence rate ratio for HCC was higher (IRR = 1.4, 95%CI: 1.1–1.9) in African Americans compared to White Americans. White Americans saw a stronger association between self-reported hepatitis C virus (aHR = 19.24, 95%CI: 10.58–35.00) and diabetes (aHR = 3.55, 95%CI: 1.96–6.43) for the development of HCC compared to African Americans (aHR = 7.73, 95%CI: 5.71–10.47 and aHR = 1.48, 95%CI: 1.06–2.06, respectively) even though the prevalence of these risk factors was similar between races. Smoking (aHR = 2.91, 95%CI: 1.87–4.52) and heavy alcohol consumption (aHR = 1.59, 95%CI: 1.19–2.11) were significantly associated with HCC risk among African Americans only. In this large prospective cohort, we observed racial differences in HCC incidence and risk factors associated with HCC among White and African Americans.

The aims of this study were to determine the incidence of external genital lesions (EGLs), specifically histologically confirmed condyloma (genital warts) and Penile Intraepithelial Neoplasia (PeIN), and genital HPV infection progression to EGLs among healthy men aged 18–73 residing in Brazil. Subjects included 1118 men enrolled in the HPV Infection in Men (HIM) study between July 2005 and June 2009. At each visit, EGLs were biopsied and subjected to pathological evaluation. HPV status in genital swabs and biopsies was determined by Linear Array and INNO-LiPA, respectively. Age-specific EGLs incidence and the proportion and median time to EGL development were estimated. Kaplan–Meier cumulative incidence rates at 6, 12, and 24 months were determined. During follow-up, 73 men developed an incident EGL. Men could develop multiple EGLs and there were 36 men with condyloma, 27 men with lesions suggestive of condyloma, six men with PeIN, and 20 men with non-HPV lesions. HPV-positive men who developed EGLs were younger (p = 0.002) than men that did not develop lesions. Among the 815 men with HPV infection, 4% progressed to EGL with the same HPV detected in the swab. During follow up, 15.7% of genital HPV-6 and HPV-11 infections progressed to condyloma (median progression time of nine months for HPV-6 versus 6.8 months for HPV-11). Approximately 1% of HPV-16 infections progressed to PeIN with a median progression time of 25 months. HPV types covered by the 4-valent HPV vaccine were detected in 82.3% and 83.3% of condyloma and PeIN, respectively. The high burden of HPV and high frequency of progression to disease underscores the need to offer HPV prophylactic vaccination to men to reduce the overall burden of infection and diseases caused by HPV. Keywords: Men, Genital lesions, PeIN, Condyloma, HPV

Background: Male genital human papillomavirus (HPV) prevalence and incidence has been reported to vary by geographical location. Our objective was to assess the natural history of genital HPV by country among men with a median of 48 months of follow-up. Methods: Men ages 18–70 years were recruited from United States (n = 1,326), Mexico (n = 1,349), and Brazil (n = 1,410). Genital specimens were collected every 6 months and HPV genotyping identified 37 HPV genotypes. Prevalence of HPV was compared between the three countries using the Fisher exact test. Incidence rates and 95% confidence intervals were calculated. The median time to HPV clearance among men with an incident infection was estimated using the Kaplan–Meier method. Results: The prevalence and incidence of the genital HPV types known to cause disease in males (HPV 16 and 6) was significantly higher among men from Brazil than men from Mexico. Prevalence and incidence of those genital HPV types in the United States varied between being comparable with those of Mexico or Brazil. Although genital HPV16 duration was significantly longer in Brazil (P = 0.04) compared with Mexico and the United States, HPV6 duration was shortest in Brazil (P = 0.03) compared with Mexico and the United States. Conclusions: Men in Brazil and Mexico often have similar, if not higher prevalence of HPV compared with men from the United States. Impact: Currently, there is no routine screening for genital HPV among males and while HPV is common in men, and most naturally clear the infection, a proportion of men do develop HPV-related diseases. Men may benefit from gender-neutral vaccine policies. Cancer Epidemiol Biomarkers Prev; 26(7); 1043–52. ©2017 AACR.

Background: HPV antibodies are a marker of past exposure to the virus. Our objective was to assess HPV serostatus pre- and post-vaccination among HIV-negative women. Methods: Women aged 16â24 years old were randomized in a placebo controlled trial utilizing the 4-valent HPV (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received the 4vHPV vaccine or placebo following a three dose schedule. Sera were collected at Day 1 and Month 7 for assessment of HPV 6, 11, 16, and 18 neutralizing antibody levels using a multiplex competitive Luminex immunoassay (Merck) based on detecting the L1 capsid antigen for each HPV type. Results: Seroprevalence was 73% for HPV6, 47% for HPV11, 33% for HPV16, and 44% for HPV18. Seroprevalence for any HPV type did not significantly differ by age or lifetime number of partners. The majority of participants (64%) had two or more 4vHPV antibodies present at enrollment and 12% had antibodies to all four. Among women in the vaccine arm, those that were seropositive for HPV16 at enrollment had higher titers at month 7 compared to women that were seronegative for HPV16 at enrollment; this trend holds for the other HPV types as well. Seroconversion among baseline seronegative participants in the placebo group ranged from 5% for HPV16 to 23% for HPV6. Conclusion: HPV seroprevalence was high in this population, emphasizing the need to vaccinate prior to sexual debut. Keywords: HPV vaccine, EVRI, Seroprevalence, cLIA

ObjectiveTo estimate the prevalence and describe the patterns of concurrent human papillomavirus (HPV) and STIs and associated factors among HIV-negative young Western Cape, South African women participating in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) trial.MethodsHIV-negative women aged 16–24 years old were enrolled in the EVRI trial (NCT01489527) and randomised to receive the licensed four-valent HPV vaccine or placebo. At study entry, participants were clinically evaluated for five STIs: herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis and disease-causing HPV genotypes (6/11/16/18/31/33/35/39/45/51/52/56/58/59/68). Demographic and sexual history characteristics were compared among women with STI co-infections, single infection and no infection using Pearson χ2and Mann-Whitney tests. ORs were calculated to evaluate factors associated with STI co-infection prevalence.ResultsAmong 388 young women, STI co-infection prevalence was high: 47% had ≥2 concurrent STIs, 36% had a single STI and 17% had none of the five evaluated STIs. HPV/HSV-2 (26%) was the most prevalent co-infection detected followed by HPV/HSV-2/Chlamydia trachomatis(CT) (17%) and HPV/CT (15%). Co-infection prevalence was independently associated with alcohol use (adjusted OR=2.01, 95% CI 1.00 to 4.06) and having a sexual partner with an STI (adjusted OR=6.96, 95% CI 1.53 to 30.08).ConclusionsAmong high-risk young women from underserved communities such as in Southern Africa, a multicomponent prevention strategy that integrates medical and behavioural interventions targeting both men and women is essential to prevent acquisition of concurrent STI infections and consequent disease.Trial registration numberNCT01489527; Post-results.

Data on cutaneous human papillomavirus (HPV) seroprevalence are primarily derived from skin cancer case–control studies. Few studies have reported the seroprevalence of cutaneous HPV among healthy men. This study investigated the seroprevalence of cutaneous HPV types and associated risk factors among men residing in Brazil, Mexico and the USA. Six hundred men were randomly selected from the HPV Infection in Men study. Archived serum specimens were tested for antibodies against 14 cutaneous HPV genotypes, β-HPV types (5/8/12/14/17/22/23/24/38/48), α-HPV 27, γ-HPV 4, µ-HPV1 and ν-HPV 41 using a glutathione S-transferase L1-based multiplex serology assay. Risk factor data were collected by a questionnaire. Binomial proportions were used to estimate seroprevalence, and logistic regression to examine factors associated with seropositivity. Overall, 65.4 % of men were seropositive to ≥1 of the 14 cutaneous HPV types, and 39.0 % were positive for ≥1 β-HPV types. Seroprevalence was 8.9, 30.9, 28.6 and 9.4 % for α-HPV 27, γ-HPV 4, µ-HPV 1 and ν-HPV 41, respectively. In multivariate analyses, seropositivity for any cutaneous HPV type was associated with higher education [adjusted odds ratio (AOR) 1.75; 95 % confidence interval (CI) 1.08–2.83], and seropositivity of any β-HPV type was significantly associated with increasing age (AOR 1.72; 95 % CI 1.12–2.63, for men aged 31–44 years vs men aged 18–30 years). Other factors associated with various type-specific cutaneous HPV seropositivity included country, circumcision and lifetime number of male sexual partners. These data indicate that exposure to cutaneous HPV is common. Future studies are needed to assess the role of cutaneous HPV in diseases.

Epidemiological characteristics of hepatocellular carcinoma (HCC) in Southern Vietnam has been well reported as in Globocan 2018 while data from the North has still not been fully presented. Therefore, we conducted this retrospective descriptive study on 198 advanced HCC patients treated at 3 major hospitals in Northern Vietnam to describe demographic features, HCC risk factors, and correlation among them in patients with advanced HCC. This information will lead to prevention efforts and provide information for allocating funds for treatment. The median age at diagnosis was 57 years (range: 19-86) and the male/female ratio was 8.9/1. The proportions of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were 81.3% and 5.6%, respectively. Hepatitis C virus infection rate was significantly higher in patients

The purpose of this study was to assess whether the incidence of histopathologically confirmed condyloma and penile intraepithelial neoplasia (PeIN) and rates of genital HPV infection progression to these lesions differs by country (Brazil, Mexico, and the U.S.). At each visit, lesions were biopsied and were categorized by pathologic diagnoses. The Linear Array genotyping method was used to identify HPV genotypes from genital swabs, while the INNO-LiPA HPV Genotyping Extra method was used for tissue specimens. Age-specific analyses were conducted for lesion incidence by country, with Kaplan–Meier estimation of cumulative incidence. The proportion of HPV infections that progressed to condyloma and PeIN, the median time to lesion development, and the incidence rates were estimated by country. When comparing demographic and sexual characteristics across the three countries, sexual orientation (p=0.008) and lifetime number of female sexual partners (p

Summary Objective The objective of this analysis was to assess human papillomavirus (HPV) infection persistence and incidence 7-months post-enrollment by HPV vaccine study arm (vaccine or placebo). Methods HIV-negative, sexually active women aged 16–24 years in the Western Cape, South Africa, were enrolled in the EVRI Trial and were randomized to receive 4-valent HPV vaccine or placebo. Cervical specimens were collected at enrollment and at the 7-month visit and were genotyped for HPV. HPV prevalence, persistence, and incidence were calculated. Prevalence ratios and odds ratios were calculated to assess factors associated with a prevalent and incident HPV infection. Results HPV incidence rates were marginally higher for the placebo group (n = 163) compared to the vaccine group (n = 169). A large proportion of the prevalent high-risk (HR-HPV) HPV types (49%) persisted over the 7-month period in both arms. Prevalent HR-HPV infection was significantly associated with a prevalent gonorrhea infection and detection of Herpes simplex type 2 antibodies. Incident HR-HPV infection was significantly associated with abnormal cervical cytology at enrollment and younger age. Conclusions Women living in geographic areas, such as southern Africa, at high-risk for HPV need to receive HPV vaccination at a very young age to maximally prevent infection and subsequent disease.

Background: Protection from naturally acquired human papillomavirus (HPV) antibodies may influence HPV infection across the lifespan. This study describes seroconversion rates following genital, anal, and oral HPV 6/11/16/18 infections in men and examines differences by HPV type and anatomic site. Methods: Men with HPV 6/11/16/18 infections who were seronegative for those genotypes at the time of DNA detection were selected from the HPV Infection in Men (HIM) Study. Sera specimens collected ≤36 months after detection were analyzed for HPV 6/11/16/18 antibodies using a virus-like particle-based ELISA. Time to seroconversion was separately assessed for each anatomic site, stratified by HPV type. Results: Seroconversion to ≥1 HPV type (6/11/16/18) in this sub-cohort (N=384) varied by anatomic site, with 6.3%, 18.9%, and 0.0% seroconverting following anal, genital, and oral HPV infection, respectively. Regardless of anatomic site, seroconversion was highest for HPV 6 (19.3%). Overall, seroconversion was highest following anal HPV 6 infection (69.2%). HPV persistence was the only factor found to influence seroconversion. Conclusions: Low seroconversion rates following HPV infection leave men susceptible to recurrent infections that can progress to HPV-related cancers. This emphasizes the need for HPV vaccination in men to ensure immune protection against new HPV infections and subsequent disease. Keywords: HPV, Men, Seroconversion, HPV antibodies, Human papillomavirus

Describe the natural history of anal HPV among men.Prospective study among men 18-70 years (n=665), from Cuernavaca, Mexico who completed questionnaires and provided specimens (HPV genotyped) at enrollment and 1+ follow-up visit. HPV prevalence and incidence were estimated. Prevalence ratios were calculated with Poisson regression using robust variance estimation. Person-time for incident HPV infection was estimated using number of events modeled as Poisson variable for total person-months.Anal infection prevalence: any HPV type=15%, high-risk=8.4%, HPV16=1.4%, tetravalent vaccine types (4vHPV)=4.4%, nonavalent vaccine types (9vHPV)=6.3%. Factors associated with prevalence: 50+ lifetime female sex partners (adjusted prevalence ratio, a PR=3.25, 95% CI:1.12- 9.47), 10+ lifetime male sex partners (aPR=3.06, 95%CI:1.4- 6.68), and 1+ recent male anal sex partners (aPR=2.28, 95%CI:1.15-4.5). Anal incidence rate: high-risk HPV=7.8/1000 person-months (95%CI:6.0-10.1), HPV16=1.8/1000 personmonths (95%CI:1.1-2.9),4vHPV=3.4/1000 person-months (95%CI:2.3-4.9) and 9vHPV=5.5/1000 person-months (95%CI:4.1-7.5).Implementation of universal HPV vaccination programs, including men, is a public health priority.Generar evidencia que apoye la vacunación universal contra VPH.Estudio prospectivo con hombres 18-70 años (n=665) de Cuernavaca, México con cuestionarios y genotipificación de VPH en muestras (2+mediciones). Se estimó prevalencia e incidencia; se calcularon tasas de prevalencia con regresión Poisson. Se estimó persona-tiempo para infecciones incidentes.Prevalencia de infección anal: cualquier tipo de VPH=15%, altoriesgo=8.4%, VPH16=1.4%, tipos en vacuna tetravalente=4.4% y tipos en vacuna nonavalente=6.3%. Factores asociados con infección prevalente: 50+ parejas sexuales femeninas en la vida (tasa de prevalencia ajustada, TPa=3.25, IC95%:1.12-9.47); 10+ parejas sexuales masculinas en la vida (TPa=3.06, IC95%:1.4- 6.68) y 1+ parejas masculinas (sexo anal) recientes (TPa=2.28, IC95%:1.15-4.5). Tasas de incidencia para infección anal: VPH alto-riesgo=7.8/1000 persona-meses (IC95%:6.0-10.1), VPH 16=1.8/1000 persona-meses (95%IC:1.1-2.9), tipos en vacuna tetravalente=3.4/1000 persona-meses y tipos en vacuna nonavalente=5.5/1000 persona-meses.mplementación de programas de vacunación universal (incluyendo hombres) contra VPH es una prioridad en salud pública.

Summary Objectives Globally, anal cancer incidence is rare, but is increasing in some world regions. Our objective was to assess differences in anal HPV natural history in three countries. Methods Men aged 18–70 years were recruited from the US (n = 634), Mexico (n = 665), and Brazil (n = 731). Anal specimens were collected every six-months. HPV genotyping was assessed by Linear Array. Anal HPV prevalence was compared using the Fisher's exact test. HPV infection incidence rates (IR) and 95% confidence intervals (CI) were calculated. Results Any anal HPV prevalence was highest among men from Brazil (24%) compared to Mexico (15%) and the US (15%). When stratified by sexual history, the prevalence of any HPV among MSM/MSMW was 43%, 37%, and 45% and 9%, 12%, and 10% for MSW from Brazil, Mexico, and US, respectively. Any HPV incidence was significantly higher among men from Brazil compared to US men (IRR = 2.4, 95% CI = 1.7–3.4) and comparable between men from Mexico and the US (IRR = 1.2, 95% CI = 0.8–1.8). Conclusion Men in Brazil and Mexico often have similar, if not higher incidence of anal HPV compared to men from the U.S., and may benefit from gender neutral HPV vaccine policies.

Human papillomaviruses (HPVs) cause cancer at multiple anatomic sites in men and women, including cervical, oropharyngeal, anal, vulvar and vaginal cancers in women and oropharyngeal, anal and penile cancers in men. In this EUROGIN 2014 roadmap, differences in HPV-related cancer and infection burden by gender and anatomic site are reviewed. The proportion of cancers attributable to HPV varies by anatomic site, with nearly 100% of cervical, 88% of anal and

HPV vaccines can prevent multiple cancers in women and men. Difficulties in the cost and completion of the three-dose vaccine series have led to considerations of alternative dose schedules. In clinical trials, three doses given within a 12-month period versus the standard 6-month period yielded comparable results, and immunogenicity appears comparable with two doses in adolescent females compared to the three-dose series in adult females. While the data are generally supportive of moving to a two-dose vaccine schedule among young female adolescents, the adoption of a two-dose vaccine schedule still poses a potential risk to the strength and longevity of the immune response. Public health authorities implementing a two-dose vaccine schedule should devise risk management strategies to minimize the potential impact on cancer prevention.

Our work aimed to examine the potential influence of variants in interleukin/interleukin receptors genes on high-risk (HR-HPV) HPV clearance. Clearance of genital HR-HPV infection was evaluated for 134 HIV-1 seropositive African-American female adolescents from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Genotyping targeted 225 single nucleotide polymorphisms (SNPs) within the exons, 5' untranslated region (UTR) and 3' UTR sequences of 27 immune-related candidate genes encoding interleukin family of cytokines. Cox proportional hazard models were used to determine the association of type-specific HPV clearance adjusting for time-varying CD4+ T-cell count and low-risk (LR-HPV) HPV co-infections. HR-HPV clearance rates were significantly (p < 0.001) associated with five SNPs (rs228942, rs419598, rs315950, rs7737000, and rs9292618) mapped to coding and regulatory regions in three genes (IL2RB, IL1RN, and IL7R). These data suggest that the analyzed genetic variants in interleukin family of cytokines modulate HR-HPV clearance in HIV-1 seropositive African-Americans that warrants replication.

To determine external genital lesion (EGL) incidence -condyloma and penile intraepithelial neoplasia (PeIN)- and genital HPV-genotype progression to these EGLs.Participants (healthy males 18- 74y from Cuernavaca, Mexico, recruited 2005-2009, n=954) underwent a questionnaire, anogenital examination, and sample collection every six months;including excision biopsy on suspicious EGL with histological confirmation.Linear array assay PCR characterized 37 high/low-risk HPV-DNA types. EGL incidence and cumulative incidence were calculated, the latter with Kaplan-Meier.EGL incidence was 1.84 (95%CI=1.42-2.39) per 100-person-years (py); 2.9% (95%CI=1.9-4.2) 12-month cumulative EGL.Highest EGL inci- dence was found in men 18-30 years:1.99 (95%CI=1.22-3.25) per 100py. Seven subjects had PeIN I-III (four with HPV16). HPV11 most commonly progresses to condyloma (6-month cumulative incidence=44.4%, 95%CI=14.3-137.8). Subject with high-risk sexual behavior had higher EGL incidence.In Mexico, anogenital HPV infection in men is high and can cause condyloma. Estimation of EGL magnitude and associated healthcare costs is necessary to assess the need for male anti-HPV vaccination.Determinar incidencia de lesiones genitales externas (LGE) –condiloma y neoplasia intraepitelial del pene (NIP)– y progresión de genotipos deVPH a LGE.Se aplicaron cuestionarios,examen anogenital y recolección de muestras cada seis meses a hombres sanos (18-74 años, de Cuernavaca, México, reclutados 2005-2009, n=954) con biopsia y confirmación histológica. Se caracteri- zaron 37 tipos de ADN-VPH; se calculó incidencia de LGE (cumulativa con Kaplan-Meier).Incidencia de LGE=1.84 (IC95%=1.42-2.39) por 100-persona-años (pa); 2.9% (IC95%=1.9-4.2) LGE acumulativa a 12 meses. Mayor incidencia de LGE entre hombres 18-30 años; 1.99 (IC95%=1.22-3.25) por 100pa.Siete sujetos tuvieron NIP I-III. VPH-11 más comúnmente progresa a condiloma (incidencia acumulativa a seis meses=44.4%, IC95%=14.3-137.8). Los sujetos con comportamiento sexual de alto riesgo tuvieron mayor incidencia de LGE.En México la infección anogenital conVPH es alta y puede causar condiloma. La estimación de magnitud de LGE y los costos sanitarios asociados se necesita para evaluar la necesidad de vacunación contra VPH en hombres.

The purpose of this study was to assess whether the incidence of histopathologically confirmed condyloma and penile intraepithelial neoplasia (PeIN) and rates of genital HPV infection progression to these lesions differs by country (Brazil, Mexico, and the U.S.). At each visit, lesions were biopsied and were categorized by pathologic diagnoses. The Linear Array genotyping method was used to identify HPV genotypes from genital swabs, while the INNO-LiPA HPV Genotyping Extra method was used for tissue specimens. Age-specific analyses were conducted for lesion incidence by country, with Kaplan–Meier estimation of cumulative incidence. The proportion of HPV infections that progressed to condyloma and PeIN, the median time to lesion development, and the incidence rates were estimated by country. When comparing demographic and sexual characteristics across the three countries, sexual orientation (p=0.008) and lifetime number of female sexual partners (p < 0.0001) were differentially associated with lesion incidence in the three countries. Condyloma incidence in Brazil and the U.S. decreased with age, while incidence remained constant across the lifespan in Mexico. There were no differences by country and age for PeIN incidence. HPV types 6 and 11 were the most common types to progress to condyloma, and HPV types 16, 6, and 11 were the most common types to progress to PeIN in all three countries. The continuous risk of condyloma and PeIN across all age groups and countries in this study emphasizes the need to ensure that strong HPV immunity, such as that obtained through vaccination, is maintained across the lifespan of men.

Our goal was to describe prevalence of β-HPVs at three anatomic sites among 717 men from Brazil, Mexico and US enrolled in the HPV Infection in Men (HIM) Study. β-HPVs were genotyped using Luminex technology. Overall, 77.7%, 54.3% and 29.3% men were positive for any β-HPV at the genitals, anal canal, and oral cavity, respectively. Men from US and Brazil were significantly less likely to have β-HPV at the anal canal than men from Mexico. Older men were more likely to have β-HPV at the anal canal compared to younger men. Prevalence of β-HPV at the oral cavity was significantly associated with country of origin and age. Current smokers were significantly less likely to have β-HPV in the oral cavity than men who never smoked. Lack of associations between β-HPV and sexual behaviors may suggest other routes of contact such as autoinoculation which need to be explored further.

Naturally induced serum antibodies against human papillomavirus (HPV) may affect risks of subsequent incident genital infections by HPV 6, 11, 16, or 18 in men. In this study, we examined the hypothesis by following 4,123 healthy men every 6 months (median follow-up time, 4.1 years). HPV antibodies were measured at baseline using a virus-like particle-based ELISA assay. Genital HPV genotypes were detected using Roche Linear Array. Incidence proportions and 6-month persistence proportions were calculated at 6-month intervals. Kaplan–Meier curves and Cox models were used to assess genotype-specific cumulative incidence and HRs, respectively. HPV 6, 11, 16, and 18 seroprevalence was 8.1%, 13.9%, 12.7%, and 10.8%, respectively. Significantly higher rates of incident infections were observed for HPV 16 among baseline-seropositive men [adjusted HR, 1.37; 95% confidence interval (CI), 1.01–1.86], with similar but nonsignificant HRs for 6-month persistent infections. Risk of persistent HPV 18 infection was significantly lower among seropositive men in the unadjusted model (HR, 0.22; 95% CI, 0.06–0.91), but not in the adjusted model (HR, 0.19; 95% CI, 0.03–1.37). Incident and 6-month persistent infections for HPV 6 and 11 did not differ by baseline serostatus. Baseline serostatus among men was not associated with a reduction in subsequent incident genital HPV 6, 11, and 16 infections. However, protection against persistent HPV18 infections was observed in unadjusted models. Our research suggests a need of further studies to examine the potentially protective effects of naturally induced HPV18 antibodies in men. Cancer Res; 76(20); 6066–75. ©2016 AACR.

Background:This study sought to assess the feasibility of conducting a phase III HIV prevention trial using a multivalent human papillomavirus (HPV) vaccine (Gardasil; Merck, Whitehouse Station, NJ).Methods:A total of 479 sexually active women aged 16-24 years in the Western Cape, South Africa, were enrolled in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) Trial. Of these, 402 were HIV negative, nonpregnant, and randomized 1:1 to receive Gardasil or a saline placebo vaccine. Vaccine doses were administered at enrollment, month 2, and month 6, and participants were followed for 1 month after the third dose. Enrollment HIV, HPV, other sexually transmitted infections (STIs), and cervical cytology were evaluated. Rates of accrual, vaccine compliance, and adherence to protocol were monitored.Results:High rates of accrual of eligible females to study (93%) and completion of the 3-dose vaccine series (91%) were noted, with few protocol violations. Ineligibility due to reported HIV positivity was 19%, and another 12% of those enrolled tested HIV positive. STI prevalence was high, with 6.2%, 10.9%, and 32.8% testing positive for syphilis, gonorrhea, and chlamydia, respectively. Cervical prevalence of 1 of 37 HPV types was 71%. STI and HPV prevalence was highest among the youngest women (

Background Human papillomavirus (HPV) causes two types of external genital lesions (EGLs) in men: genital warts (condyloma) and penile intraepithelial neoplasia (PeIN). Objective The purpose of this study was to describe genital HPV progression to a histopathologically confirmed HPV-related EGL. Design, setting, and participants A prospective analysis nested within the HPV Infection in Men (HIM) study was conducted among 3033 men. At each visit, visually distinct EGLs were biopsied; the biopsy specimens were subjected to pathologic evaluation and categorized by pathologic diagnoses. Genital swabs and biopsies were used to identify HPV types using the Linear Array genotyping method for swabs and INNO-LiPA for biopsy specimens. Outcome measurements and statistical analysis EGL incidence was determined among 1788 HPV-positive men, and cumulative incidence rates at 6, 12, and 24 mo were estimated. The proportion of HPV infections that progressed to EGL was also calculated, along with median time to EGL development. Results and limitations Among 1788 HPV-positive men, 92 developed an incident EGL during follow-up (9 PeIN and 86 condyloma). During the first 12 mo of follow-up, 16% of men with a genital HPV 6 infection developed an HPV 6-positive condyloma, and 22% of genital HPV 11 infections progressed to an HPV 11-positive condyloma. During the first 12 mo of follow-up, 0.5% of men with a genital HPV 16 infection developed an HPV 16-positive PeIN. Although we expected PeIN to be a rare event, the sample size for PeIN ( n =10) limited the types of analyses that could be performed. Conclusions Most EGLs develop following infection with HPV 6, 11, or 16, all of which could be prevented with the 4-valent HPV vaccine. Patient summary In this study, we looked at genital human papillomavirus (HPV) infections that can cause lesions in men. The HPV that we detected within the lesions could be prevented by a vaccine.

Human papillomaviruses (HPVs) cause cancer at multiple anatomic sites in men and women, including cervical, oropharyngeal, anal, vulvar, and vaginal cancers in women and oropharyngeal, anal, and penile cancers in men. In this EUROGIN 2014 roadmap, differences in HPV-related cancer and infection burden by gender and anatomic site are reviewed. The proportion of cancers attributable to HPV varies by anatomic site, with nearly 100% of cervical, 88% of anal, and less than 50% of lower genital tract and oropharyngeal cancers attributable to HPV, depending on world region and prevalence of tobacco use. Often mirroring cancer incidence rates, HPV prevalence and infection natural history varies by gender and anatomic site of infection. Oral HPV infection is rare and significantly differs by gender; yet HPV-related cancer incidence at this site is several-fold higher than at either the anal canal or penile epithelium. HPV seroprevalence is significantly higher among women compared to men, likely explaining the differences in age-specific HPV prevalence and incidence patterns observed by gender. Correspondingly, among heterosexual partners, HPV transmission appears higher from women to men. More research is needed to characterize HPV natural history at each anatomic site where HPV causes cancer in men and women, information that is critical to inform the basic science of HPV natural history and the development of future infection and cancer prevention efforts.

ObjectivesEastern Africa has the highest incidence and mortality rates from cervical cancer worldwide. It is important to describe the differences among women and their perceived risk of cervical cancer to determine target groups to increase cervical cancer screening.MethodsIn this cross-sectional study, we surveyed women seeking reproductive health services in Kisumu, Kenya to assess their perceived risk of cervical cancer and risk factors influencing cervical cancer screening uptake. χ2 statistics and t tests were used to determine significant factors, which were incorporated into a logistic model to determine factors independently associated with cervical cancer risk perception.ResultsWhereas 91% of the surveyed women had heard of cancer, only 29% of the 388 surveyed women had previously heard of cervical cancer. Most had received their information from health care workers. Few women (6%) had ever been screened for cervical cancer and cited barriers such as fear, time, and lack of knowledge about cervical cancer. Nearly all previously screened women (22/24 [92%]) believed that cervical cancer was curable if detected early and that screening should be conducted annually (86%). Most women (254/388 [65%]) felt they were at risk for cervical cancer. Women with perceived risk of cervical cancer were older (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.10), reported a history of marriage (OR, 2.08; CI, 1.00–4.30), were less likely to feel adequately informed about cervical cancer by health care providers (OR, 0.76; CI, 0.18–0.83), and more likely to intend to have cervical cancer screening in the future (OR, 10.59; CI, 3.96–28.30). Only 5% of the women reported that they would not be willing to undergo screening regardless of cost.ConclusionsCervical cancer is a major health burden for women in sub-Saharan Africa, yet only one third of the women had ever heard of cervical cancer in Kisumu, Kenya. Understanding factors associated with women’s perceived risk of cervical cancer could guide future educational and clinical interventions to increase cervical cancer screening.

Background Several studies have assessed risk factors associated with herpes simplex virus-2 (HSV-2) prevalence in adults; however, few have focused on HSV-2 incidence, particularly in adolescents. The objective of this study was to determine HSV-2 prevalence and incidence and associated risk factors in a HIV-1-positive and at risk HIV-1-negative adolescent population. Methods Sera were tested for HSV-2 antibodies in 518 adolescents in the Reaching for Excellence in Adolescent Care and Health cohort at baseline and again at the final follow-up visit. Prevalence at baseline and incidence (per person years) of HSV-2 infection were calculated. Furthermore, among HIV-1-positive individuals, a subgroup analysis was performed to assess risk factors for HSV-2 infection. Conditional logistic regression was used to estimate odds ratios and P values for associations between CD4+ T-cell (CD4+) count, HIV-1 viral load (VL), and HSV-2 acquisition, adjusting for antiretroviral therapy use, other sexually transmitted infections, gender, race, and number of sexual partners. Results At baseline, 179 (35%) subjects were HSV-2 positive, with an additional 47 (16%) new cases being identified during a median follow-up time of 1.95 years and an incidence rate of 7.35 cases per 100 person years. Several risk factors were associated with HSV-2 prevalence (being female, non-Hispanic, uncertainty of sexual preference, and HIV-1 positive) and incidence (using drugs, alcohol, and number of new sexual partners). Among HIV-1 positives, an increase in CD4+ count by 50 cell/mm(3) (odds ratio, 1.17; 95% CI, 1.04-1.31, P = 0.008) was associated with HSV-2 acquisition. Conclusions The high prevalence and incidence of HSV-2 infection among adolescents, compared with the general population at this age group suggests a critical need for screening and preventive programs among this targeted group.

Background HIV-1-positive patients clear the human papillomavirus (HPV) infection less frequently than HIV-1-negative. Datasets for estimating HPV clearance probability often have irregular measurements of HPV status and risk factors. A new transitional probability-based model for estimation of probability of HPV clearance was developed to fully incorporate information on HIV-1-related clinical data, such as CD4 counts, HIV-1 viral load (VL), highly active antiretroviral therapy (HAART), and risk factors (measured quarterly), and HPV infection status (measured at 6-month intervals). Methodology and Findings Data from 266 HIV-1-positive and 134 at-risk HIV-1-negative adolescent females from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort were used in this study. First, the associations were evaluated using the Cox proportional hazard model, and the variables that demonstrated significant effects on HPV clearance were included in transitional probability models. The new model established the efficacy of CD4 cell counts as a main clearance predictor for all type-specific HPV phylogenetic groups. The 3-month probability of HPV clearance in HIV-1-infected patients significantly increased with increasing CD4 counts for HPV16/16-like (p

Background The implementation of highly active antiretroviral therapy (HAART) among HIV-positive patients results in immune reconstitution, slower progression of HIV disease, and a decrease in the occurrence of opportunistic infections. However, the impact of HAART on cervical human papillomavirus (HPV) infection, clearance, and persistence in high-risk adolescents remains controversial. Methods HIV-positive and high-risk HIV-negative female adolescents were enrolled in the Reaching for Excellence in Adolescent Care and Health (REACH) longitudinal cohort study. At each semi-annual clinical visit, cervical lavage samples were tested for 30 HPV types. Type-specific and carcinogenic risk-specific HPV prevalence and incidence were compared in 373 eligible participants: 146 HIV-negative female adolescents with a median follow-up of 721.5 [IQR: 483-1301] days and 227 HIV-positive female adolescents. Of the 227 HIV-positive participants, a fixed set (n = 100) were examined both before and after HAART initiation; 70 were examined only before HAART initiation; and 57 were examined only after HAART initiation, with overall median follow-up of 271 [IQR: 86.5-473] and 427.25 [IQR: 200-871] days respectively for before and after HAART initiation. Results Of the 373 eligible participants, 262 (70%) were infected with at least one type of HPV at baseline, and 78 of the remaining 111 (70%) became infected with at least one type of HPV by the end of the study. Overall, the incidence and prevalence of HPV types 58, 53/66, 68/70, and 31/33/35 were much higher than the established carcinogenic and HPV vaccine types 16 and 18, especially in HIV-positive females both before and after HAART initiation. Baseline prevalence for individual high-risk HPV types ranged, depending on type, from 0.7-10%, 1-17%, and 1-18% in the HIV-negative group, the HIV-positive before HAART initiation group, and the HIV-positive after HAART initiation group, respectively. Likewise, the incidence ranged, depending on HPV type, from 0.64-9.83 cases/100 PY, 3.00-12.80 cases/100 PY, and 1.49-17.05 cases/100 PY in the three groups, respectively. The patterns of each HPV type infection, clearance, and persistence did not differ considerably before or after the introduction of HAART and were clearly independent of CD4+ change within the short post-HAART follow-up period. Conclusions HAART did not immediately affect the incidence of type-specific HPV infections within a short-period follow-up; however, future studies are warranted in larger populations to evaluate HAART's impact over longer periods.

Persistent high-risk human papillomavirus (HR-HPV) is a necessary and causal factor of cervical cancer. Most women naturally clear HPV infections; however, the biological mechanisms related to HPV pathogenesis have not been clearly elucidated. Host genetic factors that specifically regulate immune response could play an important role. All HIV-positive women in the HIV Epidemiology Research Study (HERS) with a HR-HPV infection and at least one follow-up biannual visit were included in the study. Cervicovaginal lavage samples were tested for HPV using type-specific HPV hybridization assays. Type-specific HPV clearance was defined as two consecutive HPV-negative tests after a positive test. DNA from participants was genotyped for 196,524 variants within 186 known immune related loci using the custom ImmunoChip microarray. To assess the influence of each single-nucleotide polymorphism (SNP) with HR-HPV clearance, the Cox proportional hazards model with the Wei-Lin-Weissfeld approach was used, adjusting for CD4+ count, low risk HPV (LR-HPV) co-infection, and relevant confounders. Three analytical models were performed: race-specific (African Americans (n = 258), European Americans (n = 87), Hispanics (n = 55), race-adjusted combined analysis, and meta-analysis of pooled independent race-specific analyses. Women were followed for a median time of 1,617 days. Overall, three SNPs (rs1112085, rs11102637, and rs12030900) in the MAGI-3 gene and one SNP (rs8031627) in the SMAD3 gene were associated with HR-HPV clearance (p

SummaryPersistent infection with human papillomavirus (HPV) causes essentially all precancerous cervical lesions and cervical cancer in females and thus is an important intermediate phenotype to cervical cancer. A majority of infected individuals naturally clear HPV viral infection, but the virus persists in a subset of infected hosts and the mechanism for this differential outcome is not well described. Most of the epidemiological studies have been cross-sectional in nature, and even with longitudinal studies, the definition of HPV persistence or clearance has not been well defined. There is no consensus on the correct time interval between HPV DNA tests, or how to utilize HPV persistence information in clinical management because there is no treatment for HPV. While most studies are performed with the endpoint of cancer, the intermediate phenotype has been overlooked. Epidemiological studies of HPV persistence suffer with several challenges in definitions, study designs, and analyses that undermine its importance in identifying and understanding the interactions between the viral and host genomes in the process of HPV infection pathogenesis. We have evaluated the current status of HPV persistence and provide perspectives on how the field would benefit from a research focus on intermediate phenotype in epidemiological studies.