Acquisition Of High-risk Human Papillomavirus Research Articles

The penile microbiota of Black South African men: relationship with human papillomavirus and HIV infection

BackgroundTo date, the microbiota of the human penis has been studied mostly in connection with circumcision, HIV risk and female partner bacterial vaginosis (BV). These studies have shown that male circumcision reduces penile anaerobic bacteria, that greater abundance of penile anaerobic bacteria is correlated with increased cytokine levels and greater risk of HIV infection, and that the penile microbiota is an important harbour for BV-associated bacteria. While circumcision has been shown to significantly reduce the risk of acquiring human papillomavirus (HPV) infection, the relationship of the penile microbiota with HPV is still unknown. In this study, we examined the penile microbiota of HPV-infected men as well as the impact of HIV status.ResultsThe penile skin microbiota of 238 men from Cape Town (South Africa) were profiled using Illumina sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene. Corynebacterium and Prevotella were found to be the most abundant genera. Six distinct community state types (CSTs) were identified. CST-1, dominated by Corynebacterium, corresponded to less infections with high-risk HPV (HR-HPV) relative to CSTs 2–6. Men in CST-5 had greater relative abundances of Prevotella, Clostridiales, and Porphyromonas and a lower relative abundance of Corynebacterium. Moreover, they were significantly more likely to have HPV or HR-HPV infections than men in CST-1. Using a machine learning approach, we identified greater relative abundances of the anaerobic BV-associated bacteria (Prevotella, Peptinophilus, and Dialister) and lower relative abundance of Corynebacterium in HR-HPV-infected men compared to HR-HPV-uninfected men. No association was observed between HIV and CST, although the penile microbiota of HIV-infected men had greater relative abundances of Staphylococcus compared to HIV-uninfected men.ConclusionsWe found significant differences in the penile microbiota composition of men with and without HPV and HIV infections. HIV and HR-HPV infections were strongly associated with greater relative abundances of Staphylococcus and BV-associated bacterial taxa (notably Prevotella, Peptinophilus and Dialister), respectively. It is possible that these taxa could increase susceptibility to HIV and HR-HPV acquisition, in addition to creating conditions in which infections persist. Further longitudinal studies are required to establish causal relationships and to determine the extent of the effect.

Incidence and Persistence of High-risk Anogenital Human Papillomavirus Infection Among Female Youth With and Without Perinatally Acquired Human Immunodefiency Virus Infection: A 3-year Observational Cohort Study.

Female youth with perinatally acquired human immunodeficiency virus (PHIV) may be at higher risk than uninfected youth for persistent anogenital human papillomavirus (HPV) infection, due to prolonged immunodeficiency. A 3-year cohort study was conducted between 2013 and 2017 among Thai and Vietnamese PHIV and HIV-uninfected females 12-24 years, matched by age group and number of lifetime sexual partners. For HPV genotyping, cervical and anal samples were obtained at baseline and annually. Vaginal samples were collected at baseline and every 6 months. Factors associated with high-risk HPV (HR-HPV) persistence and incidence were assessed. We enrolled 93 PHIV and 99 HIV-uninfected females. Median age was 19 (interquartile range [IQR] 18-20) years. For the 7 HR-HPV types (16, 18, 31, 33, 45, 52, 58) in the nonavalent HPV vaccine, PHIV had significantly higher incidence (P = .03) and persistence (P = .01) than HIV-uninfected youth over a 3-year period. Having HIV (adjusted hazard ratio [aHR] 2.1, 95% confidence interval [CI] 1.1-3.9) and ever using illegal substances (aHR 4.8, 95% CI 1.8-13.0) were associated with incident 7 HR-HPV infections. HIV-positive status (adjusted prevalence ratio [aPR] 2.2, 95% CI 1.5-3.2), recent alcohol use (aPR 1.75, 95% CI 1.2-2.5), and higher number of lifetime partners (aPR 2.0, 95% CI 1.4-3.1, for 3-5 partners; aPR 1.93, 95% CI 1.2-3.2, for ≥6 partners) were significantly associated with persistent 7 HR-HPV infections. Female PHIV were at higher risk of having anogenital HR-HPV acquisition and persistence. Primary and secondary prevention programs for HPV infection and HPV-related diseases should be prioritized for PHIV children and youth.

Incomplete excision of cervical intraepithelial neoplasia as a predictor of the risk of recurrent disease—a 16-year follow-up study

Women treated for high-grade cervical intraepithelial neoplasia (grade 2 or 3) are at elevated risk for developing cervical cancer. Suggested factors identifying women at highest risk for recurrence post-therapeutically include incomplete lesion excision, lesion location, size and severity, older age, treatment modality, and presence of high-risk human papilloma virus after treatment. This question has been intensively investigated over decades, but there is still substantial debate as to which of these factors or combination of factors most accurately predict treatment failure. In this study, we examine the long-term risk of residual/recurrent high-grade cervical intraepithelial neoplasia among women previously treated for cervical intraepithelial neoplasia 2/3 and how this varies according to margin status (considering also location), as well as comorbidity (conditions assumed to interact with high-risk human papilloma virus acquisition and/or cervical intraepithelial neoplasia progression), posttreatment presence of high-risk human papilloma virus, and other factors. This prospective study included 991 women with histopathologically confirmed cervical intraepithelial neoplasia 2/3 who underwent conization in 2000-2007. Information on the primary histopathologic finding, treatment modality, comorbidity, age, and high-risk human papilloma virus status during follow-up, and residual/recurrent high-grade cervical intraepithelial neoplasia was obtained from the Swedish National Cervical Screening Registry and medical records. Cumulative incidence of residual/recurrent high-grade cervical intraepithelial neoplasia was plotted on Kaplan-Meier curves, with determinants assessed by Cox regression. During a median of 10 years and maximum of 16 years offollow-up, 111 patients were diagnosed with residual/recurrent high-grade cervical intraepithelial neoplasia or worse. Women with positive/uncertain margins had a higher risk of residual/recurrent high-grade cervical intraepithelial neoplasia or worse than women with negative margins, adjusting for potential confounders (hazard ratio, 2.67; 95% confidence interval, 1.81-3.93). The risk of residual/recurrent high-grade cervical intraepithelial neoplasia or worse varied by anatomical localization of the margins (endocervical: hazard ratio, 2.72; 95% confidence interval, 1.67-4.41) and both endo- and ectocervical (hazard ratio, 4.98; 95% confidence interval, 2.85-8.71). The risk did not increase significantly when only ectocervical margins were positive or uncertain. The presence of comorbidity (autoimmune disease, human immunodeficiency viral infection, hepatitis B and/or C, malignancy, diabetes, genetic disorder, and/or organ transplant) was also a significant independent predictor of residual/recurrent high-grade cervical intraepithelial neoplasia or worse. In women with positive high-risk human papilloma virus findings during follow-up, the hazard ratio of positive/uncertain margins for recurrent/residual high-grade cervical intraepithelial neoplasia or worse increased significantly compared to that in women with positive high-risk human papilloma virus findings but negative margins. Patients with incompletely excised cervical intraepithelial neoplasia 2/3 are at increased risk for residual/recurrent high-grade cervical intraepithelial neoplasia or worse. Margin status combined with high-risk human papilloma virus results and consideration of comorbidity may increase the accuracy for predicting treatment failure.

High-risk human papillomavirus infection and abnormal cervical cytology among Nepali and Bhutanese refugee women living in eastern Nepal

BackgroundCervical cancer is the leading cause of cancer morbidity and mortality among women in Nepal and Bhutan. Data on high-risk human papillomavirus (HR-HPV) infection and cervical abnormalities among Nepali and Bhutanese women are sparse. The objectives of this study were to assess and compare the prevalence of HR-HPV infection and cervical abnormalities among Nepali and Bhutanese women living in Jhapa District in eastern Nepal; and examine the risk factors for HR-HPV infection and cervical abnormalities in those women.MethodsStudy participants were recruited from a women’s health camp organized by NFCC-International, a Nepal-based non-governmental organization, in 2014. Consenting participants were administered a demographic and health questionnaire and cervico-vaginal specimens collected. Both self-collected and clinician-collected cervico-vaginal specimens were tested for HR-HPV infection. Cytologic exam was performed on clinician-collected samples and cervical cytology results were categorized according to the Bethesda classification. A participant was classified as a Bhutanese if they were either born in Bhutan or currently lived in one of the United Nations administered Bhutanese refugee camps in Jhapa; otherwise, the participant was classified as a Nepali.ResultsOf the 647 study participants, 15.9% were Bhutanese women living in refugee camps and the overall age (± standard deviation) was 38.8 ± 8.2 years. The prevalence of HR-HPV infection was 8.9% and abnormal cervical cytology was 7.1% respectively, with no significant difference in HR-HPV positivity (p = 0.399) or abnormal cervical cytology (p = 0.698) between Nepali and Bhutanese women. Compared to women whose husbands had not migrated for employment, women whose husbands had migrated outside of the district had 3.30 times (95% Confidence Interval [CI]: 1.13–9.64) the odds of being HR-HPV positive and women whose husbands had migrated outside the country had 2.92 times (95% CI: 1.32–6.49) the odds of having abnormal cervical cytology.ConclusionsHR-HPV positivity and abnormal cervical cytology were similar among Nepali and Bhutanese women. Husbands migrating for employment within or outside the country was a significant risk factor for high-risk HPV infection and cervical cytology, indicating the important role spousal behavior may play in HR-HPV acquisition and cervical abnormalities among these women.

Male circumcision reduces penile high-risk human papillomavirus viral load in a randomised clinical trial in Rakai, Uganda

ObjectivesMale circumcision reduces penile high-risk human papillomavirus (HR-HPV) prevalence in randomised trials. The goal of this study was to examine the effect of circumcision on HPV viral load among HPV-infected...

Human papillomavirus incidence and clearance among HIV-positive and HIV-negative men in sub-Saharan Africa

High-risk human papillomavirus (HR-HPV) infection is the most common sexually transmitted infection. Penile and cervical cancer rates are highest in sub-Saharan Africa. However, little is known about the impact of HIV infection on HR-HPV acquisition and clearance among heterosexual men. HR-HPV incidence and clearance were evaluated in 999 men (776 HIV-negative and 223 HIV-positive) aged 15-49 years who participated in male circumcision trials in Rakai, Uganda. Penile swabs were tested for HR-HPV by Roche HPV Linear Array. A Poisson multivariable model was used to estimate adjusted incidence rate ratios (adjIRRs) and clearance risk ratios (adjRRs). HR-HPV incidence was 66.5/100 person-years in HIV-positive men and 32.9/100 person-years among HIV-negative men [IRR=2.02, 95% confidence interval (CI) 1.67-2.44]. Incidence was higher in the unmarried men (adjIRR=1.73, 95% CI 1.19-2.52), and decreased with age (adjIRR for men >35 years=0.64, 95% CI 0.43-0.94) and male circumcision (adjIRR=0.70, 95% CI 0.55-0.89). HR-HPV clearance was 114.7/100 person-years for HIV-positive men and 170.2/100 person-years for HIV-negative men (risk ratio=0.67, 95% CI 0.59-0.77). HR-HPV clearance in HIV-negative men increased with circumcision (adjRR=1.48, 95% CI 1.26-1.74), HSV-2 infection (adjRR=1.20, 95% CI 1.01-1.44), and symptoms of urethral discharge (adjRR=1.35, 95% CI 1.06-1.73). Clearance of HR-HPV was significantly lower for unmarried men (adjRR 0.76, 95% CI 0.59-0.98). HR-HPV is common among heterosexual Ugandan men, particularly the HIV-infected. HIV infection increases HR-HPV acquisition and reduces HR-HPV clearance. Promotion of male circumcision and additional prevention measures, such as HPV vaccination, is critical in sub-Saharan Africa.

Male Circumcision Decreases Acquisition and Increases Clearance of High‐Risk Human Papillomavirus in HIV‐Negative Men: A Randomized Trial in Rakai, Uganda

Uncircumcised human immunodeficiency virus (HIV)-negative men aged 15-49 years were randomized to immediate circumcision (intervention arm, 441 subjects) or delayed circumcision (control arm, 399 subjects). Human papillomavirus (HPV) was detected by Roche HPV Linear Array at enrollment, and at 6, 12, and 24 months. Incident high-risk HPV (HR-HPV) was estimated in men who acquired a new HR-HPV genotype. HR-HPV clearance was determined in men with prior genotype-specific HR-HPV infections. Rate ratios (RRs) and 95% confidence intervals (CIs) of HR-HPV acquisition were estimated by Poisson multiple regression. Enrollment characteristics were comparable between study groups. HR-HPV incidence was 19.7 cases per 100 person-years (PYs) in the intervention arm (70 cases per 355.8 PYs) and 29.4 cases per 100 PYs (125 cases per 424.8 PYs) in the control arm (RR, 0.67; 95% CI, 0.51-0.89; P = .006). The incidence of multiple HR-HPV infections was 6.7 cases per 100 PYs in the intervention arm and 14.8 cases per 100 PYs in the control arm (RR, 0.45; 95% CI, 0.28-0.73), but there was no significant effect on single infections (RR, 0.89; 95% CI, 0.60-1.30). HR-HPV incidence was lower in the intervention arm for all genotypes and demographic/behavioral subgroups. The clearance of preexisting HR-HPV infections was 215.8 cases per 100 PYs (205 cases per 95 PYs) in the intervention arm and 159.1 cases per 100 PYs (255 cases per 160.25 PYs) in the control arm (adjusted RR, 1.39; 95% CI, 1.17-1.64). Male circumcision reduces the incidence of multiple HR-HPV infections and increases clearance of HR-HPV infections in HIV-uninfected men. ClinicalTrials.gov identifier: NCT00425984 .

Association of Sexual Abuse With Incident High-Risk Human Papillomavirus Infection Among Young African-American Women

Genital human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Noticeably absent from the known risk factors for HPV infection is history of sexual abuse. The current study examined the association between sexual abuse and incident high-risk HPV among young adult black women. This longitudinal study was part of a larger HIV/STI randomized controlled behavioral trial that randomly recruited eligible participants from October 2002 through March 2006. At baseline and 12-month follow-up, 665 black women, aged between 18 and 29, completed a survey assessing known HPV risk factors and history of sexual abuse, and provided specimens that were assayed for high-risk HPV. Incident high-risk HPV infection was defined as a laboratory-confirmed test for high-risk HPV at 12-month follow-up after testing HPV-negative at baseline. The prevalence of high-risk HPV was 38.9%. Age-stratified multiple regression analyses examined sexual abuse that occurred during the 12-month follow-up and acquisition of high-risk HPV; known risk factors for HPV were entered as covariates. Women aged between 18 and 24 with a history of sexual abuse in the past year, compared with participants without a history, were 4.5 times more likely to test positive for an incident high-risk HPV infection (P <0.007). This relationship was not significant for the overall sample or for women aged between 25 and 29 years. This is one of the first analyses demonstrating exposure to sexual abuse as a predictor of high-risk HPV. HPV vaccination recommendations for black women, 18 to 24 years of age, with a history of sexual abuse warrant special consideration.

Acquisition of High-Risk Human Papillomavirus Infection in a Population-Based Cohort of Danish Women

Human papillomavirus (HPV) is the cause of cervical cancer. To better understand the natural history of HPV, we assessed the incidence of type-specific HPV infection and examined risk factors for acquisition of high-risk (HR) HPV infection in Danish women. A population-based prospective cohort study of women aged 20 to 29 years was conducted. Participants were interviewed and underwent 2 gynaecological examinations 2 years apart. Women for whom Hybrid Capture 2 results were available at both visits were included in the analysis (n = 7454). A HR HPV infection was acquired by 12.8% of the women during follow-up. The incidence decreased with increasing age. The commonest types were HPV16, HPV31, and HPV52. HPV66, HPV58, and HPV53 were mainly acquired with other HR types. Multiple HR types were acquired in 50% of the women who became HPV-positive during follow-up. In initially HPV-negative women age, number of sexual partners, and oral contraceptive use were the main risk factors for acquisition, particularly of multiple HR HPV types. HPV infections were commonly acquired. We confirmed the sexually transmitted nature of the infection. Our findings show that both the level of potential exposure and other behavioral factors increase the risk for HR HPV acquisition.

Prevalence of high‐risk human papillomavirus type 16/18 infection among women with normal cytology: risk factor analysis and implications for screening and prophylaxis

To determine the prevalence of high-risk human papillomavirus (HR-HPV) 16/18 infection of uterine cervix among women in the reproductive age group, with cytologically normal cervical (Pap) smears; to analyse the risk factors for HR-HPV acquisition and to address their implications for cervical cancer screening and prophylaxis in a low resource setting. Cervical samples from 769 cytologically negative women (age 18-45 years) attending a tertiary care centre in Delhi were subjected to HPV DNA testing and HR-HPV 16/18 and low-risk (LR)-HPV 6/11 sub-typing by polymerase chain reaction. Univariate risk factor analysis was carried out in HR-HPV positive (n = 86) versus HR-HPV negative women (n = 683) by chi-square test. The overall HPV prevalence among cytologically normal women was 16.6%. HR-HPV16 was detected in 10.1%, whereas HPV18 was detected in 1% of women. HR-HPV 16/18 comprised 67% of the total HPV positives. There was no decline in HR-HPV positivity with age, and women aged 40-44 years were at significantly increased risk for HR-HPV prevalence (P = 0.03). Statistically significant associations of HR-HPV infection were found with risk factors such as high parity (P = 0.04), cervicitis/hypertrophic cervix (P = 0.01), unhealthy cervix (P = 0.04), rural residence (P = 0.03), low socioeconomic status (P = 0.01) and illiteracy (P = 0.07). Although the sample size was small, based on the observation that HR-HPV 16 and 18 contributed significantly to the overall HPV prevalence in our setting, we speculate that testing/prophylaxis for these prevalent high-risk types could perhaps make cervical cancer screening and preventive programmes cost-effective. Larger community-based studies on HPV prevalence and persistence are required to validate these findings before definitive recommendations can be made to the policy makers.