Human papillomavirus infection: Epidemiology, biology, host interactions, cancer development, prevention, and therapeutics.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections worldwide. It is caused by the HPV, a DNA virus that infects epithelial cells in various mucous membranes and skin surfaces. HPV can be categorised into high-risk and low-risk types based on their association with the development of certain cancers. High-risk HPV types, such as HPV-16 and HPV-18, are known to be oncogenic and are strongly associated with the development of cervical, anal, vaginal, vulvar, penile, and oropharyngeal cancers. These types of HPV can persist in the body for an extended period and, in some cases, lead to the formation of precancerous lesions that may progress to cancer if left untreated. Low-risk HPV types, such as HPV-6 and HPV-11, are not typically associated with cancer but can cause benign conditions like genital warts. Genital warts are characterised by the growth of small, cauliflower-like bumps on the genital and anal areas. Although not life-threatening, they can cause discomfort and psychological distress. HPV is primarily transmitted through sexual contact, including vaginal, anal, and oral sex. It can also be transmitted through non-penetrative sexual activities that involve skin-to-skin contact. In addition to sexual transmission, vertical transmission from mother to child during childbirth is possible but relatively rare. Prevention of HPV infection includes vaccination and safe sexual practices. HPV vaccines, such as Gardasil and Cervarix, are highly effective in preventing infection with the most common high-risk HPV types. These vaccines are typically administered to adolescents and young adults before they become sexually active. Safe sexual practices, such as consistent and correct condom use and limiting the number of sexual partners, can also reduce the risk of HPV transmission. Diagnosis of HPV infection can be challenging because the infection is often asymptomatic, especially in men. In women, HPV testing can be done through cervical screening programs, which involve the collection of cervical cells for analysis. Abnormal results may lead to further diagnostic procedures, such as colposcopy or biopsy, to detect precancerous or cancerous changes. Overall, HPV infection is a prevalent sexually transmitted infection with significant implications for public health. Vaccination, regular screening, and early treatment of precancerous lesions are key strategies to reduce the burden of HPV-related diseases and their associated complications. Education and awareness about HPV and its prevention are crucial in promoting optimal sexual health. This study aimed to carry out a literature review considering several aspects involving HPV infection: Global distribution, prevalence, biology, host interactions, cancer development, prevention, therapeutics, coinfection with other viruses, coinfection with bacteria, association with head and neck squamous cell carcinomas, and association with anal cancer.

Human papillomavirus infection (HPV) and pregnancy.

Human papillomavirus (HPV) is the most common sexually transmitted viral infection worldwide, which may result in the development in benign lesions or malignant tumors. The prevalence of HPV infection is twice as high in pregnancy as in non-pregnant women. Additionally, there is a risk of vertical transmission of HPV from mother to fetus during pregnancy or childbirth. Various studies have reported an increased risk of adverse pregnancy outcomes in HPV-positive women, including miscarriage, preterm birth, premature rupture of membranes, preeclampsia, fetal growth restriction, and fetal death. HPV vaccination is not currently recommended during pregnancy. On the other hand, there is no evidence linking HPV vaccination during pregnancy with adverse pregnancy outcomes and termination of pregnancy is not justified in this case.

Public health impact and cost effectiveness of routine and catch-up vaccination of girls and women with a nine-valent HPV vaccine in Japan: a model-based study.

BACKGROUND: Combined with cancer screening programs, vaccination against human papillomavirus (HPV) can significantly reduce the high health and economic burden of HPV-related disease in Japan. The objective of this study was to assess the health impact and cost effectiveness of routine and catch-up vaccination of girls and women aged 11-26 years with a 4-valent (4vHPV) or 9-valent HPV (9vHPV) vaccine in Japan compared with no vaccination. METHODS: We used a mathematical model adapted to the population and healthcare settings in Japan. We compared no vaccination and routine vaccination of 12-16-year old girls with 1) 4vHPV vaccine, 2) 9vHPV vaccine, and 3) 9vHPV vaccine in addition to a temporary catch-up vaccination of 17-26 years old girls and women with 9vHPV. We estimated the expected number of disease cases and deaths, discounted (at 2% per year) future costs (in 2020 ¥) and discounted quality-adjusted life years (QALY), and incremental cost effectiveness ratios (ICER) of each strategy over a time horizon of 100 years. To test the robustness of the conclusions, we conducted scenario and sensitivity analyses. RESULTS: Over 100 years, compared with no vaccination, 9vHPV vaccination was projected to reduce the incidence of 9vHPV-related cervical cancer by 86% (from 15.24 new cases per 100,000 women in 2021 to 2.02 in 2121). A greater number of cervical cancer cases (484,248) and cancer-related deaths (50,102) were avoided through the described catch-up vaccination program. Routine HPV vaccination with 4vHPV or 9vHPV vaccine prevented 5,521,000 cases of anogenital warts among women and men. Around 23,520 and 21,400 diagnosed non-cervical cancers are prevented by catch-up vaccination among women and men, respectively. Compared with no vaccination, the ICER of 4vHPV vaccination was ¥975,364/QALY. Compared to 4vHPV, 9vHPV + Catch-up had an ICER of ¥1,534,493/QALY. CONCLUSIONS: A vaccination program with a 9-valent vaccine targeting 12 to 16 year-old girls together with a temporary catchup program will avert significant numbers of cases of HPV-related diseases among both men and women. Furthermore, such a program was the most cost effective among the vaccination strategies we considered, with an ICER well below a threshold of ¥5000,000/QALY.

Vorinostat, a pan-HDAC inhibitor, abrogates productive HPV-18 DNA amplification.

Human papillomaviruses (HPVs) cause epithelial proliferative diseases. Persistent infection of the mucosal epithelia by the high-risk genotypes can progress to high-grade dysplasia and cancers. Viral transcription and protein activities are intimately linked to regulation by histone acetyltransferases and histone deacetylases (HDACs) that remodel chromatin and regulate gene expression. HDACs are also essential to remodel and repair replicating chromatin to enable the progression of replication forks. As such, Vorinostat (suberoylanilide hydroximic acid), and other pan-HDAC inhibitors, are used to treat lymphomas. Here, we investigated the effects of Vorinostat on productive infection of the high-risk HPV-18 in organotypic cultures of primary human keratinocytes. HPV DNA amplifies in the postmitotic, differentiated cells of squamous epithelia, in which the viral oncoproteins E7 and E6 establish a permissive milieu by destabilizing major tumor suppressors, the pRB family proteins and p53, respectively. We showed that Vorinostat significantly reduced these E6 and E7 activities, abrogated viral DNA amplification, and inhibited host DNA replication. The E7-induced DNA damage response, which is critical for both events, was also compromised. Consequently, Vorinostat exposure led to DNA damage and triggered apoptosis in HPV-infected, differentiated cells, whereas uninfected tissues were spared. Apoptosis was attributed to highly elevated proapoptotic Bim isoforms that are known to be repressed by EZH2 in a repressor complex containing HDACs. Two other HDAC inhibitors, Belinostat and Panobinostat, also inhibited viral DNA amplification and cause apoptosis. We suggest that HDAC inhibitors are promising therapeutic agents to treat benign HPV infections, abrogate progeny virus production, and hence interrupt transmission.

Directionality of Genital Human Papillomavirus Infection Transmission Within Heterosexual Couples: A Systematic Review and Meta-analysis.

BACKGROUND: Limited evidence indicates greater female-to-male (F-M) transmission of genital infection with human papillomavirus (HPV) relative to male-to-female (M-F). We verified the hypothesis of a differential transmission rate in couple-based studies by conducting a systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, Scopus, and Cochrane Library databases for studies published until December 2019. We calculated pooled estimates of F-M and M-F transmission rates and their rate differences per 100 person-months, with 95% confidence intervals (CI), using a random-effects model. We counted occurrences of directionality preponderance for each HPV type. RESULTS: We identified 7 eligible studies published between 2008 and 2019, providing data for 752 couples. Pooled estimates for F-M and M-F transmission rates were 3.01 (95% CI, 1.19-7.64; I2 = 97%) and 1.60 (95% CI, 0.86-2.98; I2 = 89%), respectively. The overall rate difference was 0.61 (95% CI, -0.27 to 1.49; I2 = 75%). Three studies provided rates by sex and HPV genotype; 2 favored a preponderance of F-M and 1 favored M-F transmission. CONCLUSIONS: There was slight evidence for a differential transmission rate favoring higher F-M than M-F transmission with substantial statistical heterogeneity across studies.

The ability of two chlorine dioxide chemistries to inactivate human papillomavirus-contaminated endocavitary ultrasound probes and nasendoscopes.

Sexual transmission is the most common pathway for the spread of Human papillomavirus (HPV). However, the potential for iatrogenic HPV infections is also real. Even though cleared by the Food and Drug Administration and recommended by the World Federation for Ultrasound in Medicine and Biology, several disinfectants including glutaraldehyde and o-phthalaldehyde have shown a lack of efficacy for inactivating HPV. Other methods such as ultraviolet C and concentrated hydrogen peroxide have been shown highly effective at inactivating infectious HPV. In this study, two chlorine dioxide systems are also shown to be highly efficacious at inactivating HPV. An important difference in these present studies is that as opposed to testing in suspension or using a carrier, we dried the infectious virus directly onto endocavitary ultrasound probes and nasendoscopes, therefore, validating a more realistic system to demonstrate disinfectant efficacy.

Call to action for health systems integration of point-of-care testing to mitigate the transmission and burden of sexually transmitted infections.

OBJECTIVES: In 2016, WHO estimated 376 million new cases of the four main curable STIs: gonorrhoea, chlamydia, trichomoniasis and syphilis. Further, an estimated 290 million women are infected with human papillomavirus. STIs may lead to severe reproductive health sequelae. Low-income and middle-income countries carry the highest global burden of STIs. A large proportion of urogenital and the vast majority of extragenital non-viral STI cases are asymptomatic. Screening key populations and early and accurate diagnosis are important to provide correct treatment and to control the spread of STIs. This article paints a picture of the state of technology of STI point-of-care testing (POCT) and its implications for health system integration. METHODS: The material for the STI POCT landscape was gathered from publicly available information, published and unpublished reports and prospectuses, and interviews with developers and manufacturers. RESULTS: The development of STI POCT is moving rapidly, and there are much more tests in the pipeline than in 2014, when the first STI POCT landscape analysis was published on the website of WHO. Several of the available tests need to be evaluated independently both in the laboratory and, of particular importance, in different points of care. CONCLUSION: This article reiterates the importance of accurate, rapid and affordable POCT to reach universal health coverage. While highlighting the rapid technical advances in this area, we argue that insufficient attention is being paid to health systems capacity and conditions to ensure the swift and rapid integration of current and future STI POCT. Unless the complexity of health systems, including context, institutions, adoption systems and problem perception, are recognised and mapped, simplistic approaches to policy design and programme implementation will result in poor realisation of intended outcomes and impact.

Recent Penile Sexual Contact Is Associated With an Increased Odds of High-Risk Cervical Human Papillomavirus Infection in Transgender Men.

BACKGROUND: Transgender men (TM) have a male, masculine, or nonfemale gender identity, yet were assigned female sex at birth on the basis of their external genitalia. The majority of TM are at risk of infection with one of several high-risk strains of the human papillomavirus (hr-HPV), acquired primarily through sexual contact, that cause 99.7% of cervical cancers. This study aimed to explore the association between sexual behaviors and current cervical hr-HPV infection in TM with a cervix. METHODS: The primary aim of this analysis was to test for an association between participant self-report of sexual contact with a penis in the past 1 year and current infection with cervical hr-HPV as measured by provider-collected cervical HPV DNA assay. This is a secondary analysis of a bio-behavioral sexual health study conducted at a health center in Boston, MA from 2015 to 2016. Analysis was conducted using logistic regression with significance level set at P less than 0.05; the primary analysis was adjusted for self-reported age, current tobacco use, years of testosterone use, and HPV vaccination status. RESULTS: Overall prevalence of hr-HPV was 15.9%. In adjusted analyses, participants reporting receptive penile vaginal sex with any of their most recent 3 sexual partners in the past 12 months had more than 5 times greater odds of current hr-HPV infection than those reporting no penile sex of any kind during this timeframe (odds ratio, 5.23; 95% confidence interval, 1.61-17.02). CONCLUSIONS: Vaginal-receptive penile sex in the last 12 months was associated with a 5-fold increased odds of cervical high-risk HPV infection among TM. Findings can inform future population level study of associations between sexual behaviors and hr-HPV risk, which could lead to more individualized approaches to screening.

Human papillomavirus and surgical smoke: a systematic review.

OBJECTIVE: To evaluate what is currently known about the risk to surgeons and other operating theatre (OT) staff of human papillomavirus (HPV) transmission and HPV-related disease following surgical smoke exposure. METHODS: A systematic literature search of Embase and Ovid-MEDLINE was undertaken for primary studies relevant to the presence of HPV in surgical smoke, contamination of OT staff with HPV after performing or attending smoke-generating surgical procedures, and the presence of HPV or HPV-related disease in OT staff following occupational surgical smoke exposure. Additional articles were identified by searching the reference lists of relevant published papers. RESULTS: Twenty-one relevant articles were identified. These demonstrate that surgical smoke from the treatment of HPV-related lesions can contain HPV DNA, and that this can contaminate the upper airways of OT staff. Whether this corresponds to infectious virus is not known. Increased prevalence of HPV infection or HPV-related disease in OT staff following occupational exposure to surgical smoke has not been convincingly shown. CONCLUSIONS: While HPV transmission to OT staff from surgical smoke remains unproven, it would be safest to treat surgical smoke as potentially infectious. Necessary precautions should be taken when performing smoke-generating procedures, consisting of: (1) local exhaust ventilation, (2) general room ventilation and (3) full personal protective equipment including a fit tested particulate respirator of at least N95 grade. There is currently insufficient evidence to recommend HPV vaccination for OT staff or to state that the above precautions, when used properly, would not be effective at preventing HPV transmission from surgical smoke.

Laser Plume From Human Papillomavirus-Infected Tissue: A Systematic Review.

BACKGROUND: Laser procedures are becoming more prevalent across multiple medical specialties for a variety of indications. The plumes created by these lasers have raised concern for the dissemination of an infectious material. OBJECTIVE: To review and summarize the information on viral dissemination in laser plumes available in the literature. MATERIALS AND METHODS: Data Sources A systematic review was performed on English and non-English articles using the PubMed and the Cochrane databases. A manual search of bibliographies from relevant articles was also performed to collect additional studies. STUDY SELECTION: Only articles in the English language with full texts available that pertained to viral particles in laser plumes were included. Data Extraction Two authors performed independent article selections using predefined inclusion and exclusion criteria. RESULTS: There have been case reports of possible transmission of human papillomavirus (HPV) by inhalation of laser-produced aerosols. Multiple investigators have attempted to recreate this scenario in the laboratory to qualify this risk. Others have conducted clinical experiments to determine the presence of HPV in laser plumes. CONCLUSION: The current body of the literature suggests that laser surgeons are at a risk for HPV exposure by inhalation of laser-derived aerosols. We offer best practice recommendations for laser operators.

Awareness and knowledge of human papilloma virus in UK women aged 25 years and over: Results from a cross-sectional internet-based survey.

OBJECTIVE: The expanding use of human papilloma virus (HPV) testing within cervical screening requires an evaluation of public understanding of HPV. This study aimed to explore HPV awareness and knowledge using a previously psychometrically validated measure in a sample of UK women aged 25 years and over. METHODS: An anonymous web-based cross-sectional survey design was used, and responses were recorded for 246 women (mean age = 37.59, SD = 9.20). RESULTS: Findings indicated limits to women's understanding of HPV, its transmission, treatment and link with cancer. The mean HPV knowledge score was 9.35 (4.43), and the mean HPV testing score was 3.34 (1.91). Multivariate analyses revealed that information seeking following cervical screening and being a student is associated with higher HPV knowledge and that having a positive HPV test result and having university education is associated with higher HPV testing knowledge. CONCLUSIONS: These results highlight that there is a lack of knowledge and misunderstanding relating to HPV and its link with cancer in adult women in the UK. The findings suggest that public health HPV information campaigns are urgently needed, especially with a drop in UK cervical screening attendance rates, and with the upcoming change to HPV primary testing within the UK NHS cervical screening programme.

Recurring infection with ecologically distinct HPV types can explain high prevalence and diversity.

The high prevalence of human papillomavirus (HPV), the most common sexually transmitted infection, arises from the coexistence of over 200 genetically distinct types. Accurately predicting the impact of vaccines that target multiple types requires understanding the factors that determine HPV diversity. The diversity of many pathogens is driven by type-specific or "homologous" immunity, which promotes the spread of variants to which hosts have little immunity. To test for homologous immunity and to identify mechanisms determining HPV transmission, we fitted nonlinear mechanistic models to longitudinal data on genital infections in unvaccinated men. Our results provide no evidence for homologous immunity, instead showing that infection with one HPV type strongly increases the risk of infection with that type for years afterward. For HPV16, the type responsible for most HPV-related cancers, an initial infection increases the 1-year probability of reinfection by 20-fold, and the probability of reinfection remains 14-fold higher 2 years later. This increased risk occurs in both sexually active and celibate men, suggesting that it arises from autoinoculation, episodic reactivation of latent virus, or both. Overall, our results suggest that high HPV prevalence and diversity can be explained by a combination of a lack of homologous immunity, frequent reinfections, weak competition between types, and variation in type fitness between host subpopulations. Because of the high risk of reinfection, vaccinating boys who have not yet been exposed may be crucial to reduce prevalence, but our results suggest that there may also be large benefits to vaccinating previously infected individuals.

Impact of COVID-19 and other viruses on reproductive health.

Male infertility is linked to some viral infections including human papillomavirus (HPV), herpes simplex viruses (HSV) and human immunodeficiency viruses (HIVs). Almost nothing is known about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effect on fertility. The possible risk factors of coronavirus disease 2019 (COVID-19) infection on fertility comes from the abundance of angiotensin-Converting Enzyme-2 (ACE2), receptor entry of the virus, on testes, a reduction in important sex hormone ratios and COVID-19-associated fever. Recent studies have shown a gender difference for COVID-19 rates and comorbidity. In this review, we will discuss the potential effect of COVID-19 on male fertility and talk about what needs to be done by the scientific community to tackle our limited understanding of the disease. On the other side, we will focus on what is known so far about the risk of COVID-19 on pregnancy, neonatal health and the vertical transfer of the virus between mothers and their neonates. Finally, because reproduction is a human right and infertility is considered a health disease, we will discuss how assisted reproductive clinics can cope with the pandemic and what guidelines they should follow to minimise the risk of viral transmission.

HPV vaccine, Twitter, and gay, bisexual and other men who have sex with men.

This study aimed to quantify human papillomavirus (HPV) vaccine Twitter messaging addressing gay, bisexual and other men who have sex with men (GB+MSM) and describes messaging by vaccine sentiment (attitudes towards vaccine) and characteristics (topic of messaging). Between August 2014 and July 2015, we collected 193 379 HPV-related tweets and classified them by vaccine sentiment and characteristics. We analysed a subsample of tweets containing the terms 'gay', 'bisexual' and 'MSM' (N = 2306), and analysed distributions of sentiment and characteristics using chi-square. HPV-related tweets containing GB+MSM terms occupied 1% of our sample. The subsample had a largely positive vaccine sentiment. However, a proportion of 'gay' and 'bisexual' tweets did not mention the vaccine, and a proportion of 'gay' and 'MSM' tweets had a negative sentiment. Topics varied by GB+MSM term-HPV risk messaging was prevalent in 'bisexual' (25%) tweets, and HPV transmission through sex/promiscuity messaging was prevalent in 'gay' (18%) tweets. Prevention/protection messaging was prevalent only in 'MSM' tweets (49%). Although HPV vaccine sentiment was positive in GB+MSM messaging, we identified deficits in the volume of GB+MSM messaging, a lack of focus on vaccination, and a proportion of negative tweets. While HPV vaccine promotion has historically focused on heterosexual HPV transmission, there are opportunities to shape vaccine uptake in GB+MSM through public health agenda setting using social media messaging that increases knowledge and minimizes HPV vaccine stigma. Social media-based HPV vaccine promotion should also address the identities of those at risk to bolster vaccine uptake and reduce the risk of HPV-attributable cancers.

Sexually Transmitted Infections: Part I: Genital Bumps and Genital Ulcers.

Sexually transmitted infections (STIs) affect young people in a disproportionate way, with more than half of the infections occurring in 15- to 25-year-olds, although as an age group they constitute only 25% of the sexually active population. Pediatricians should be familiar with the social, behavioral, and biological factors that predispose adolescents to STIs. Preventive visits for teens and pre-teens should incorporate education and counseling about sexuality, safe sexual behavior, and STIs. Pediatricians should be able to identify, diagnose, and manage STIs presenting as genital "bumps" and genital "ulcers." Pediatricians should also offer human immunodeficiency virus testing and expedited partner treatment to all adolescents who are diagnosed as having an STI.

Human Papillomavirus Viral Load and Transmission in Young, Recently Formed Heterosexual Couples.

BACKGROUND: We studied the association between human papillomavirus (HPV) viral load (VL) and HPV concordance. METHODS: The HITCH cohort study included young, heterosexual, recently formed, sexually active couples. Questionnaires and genital samples were collected at 0 and 4 months. Samples were tested for HPV DNA by polymerase chain reaction (PCR; Linear Array). VLs of HPV6/11/16/18/31/42/51 were quantified using type-specific real-time PCR. Correlations between VL and type-specific HPV prevalence and incidence were evaluated using multilevel, mixed-effects linear/logistic regression models. RESULTS: We included 492 couples. VLs were higher in penile than vaginal samples. VL at subsequent visits correlated significantly within men (r, 0.373), within women (r, 0.193), and within couples (r range: 0.303-0.328). Men with high VL had more type-specific persistent HPV infections (odds ratio [OR], 4.6 [95% confidence interval {CI}, 2.0-10.5]). High VL in men was associated with prevalent (OR, 5.3 [95% CI, 2.5-11.2]) and incident (OR, 6.7 [95% CI, 1.5-30.7]) type-specific HPV infections in their partner. Women's VL was associated with type-specific HPV prevalence in their partner at the same (OR, 5.9) and subsequent (OR, 4.7) visit. CONCLUSIONS: Persistent HPV infections have limited VL fluctuations. VL between sex partners are correlated and seem predictive of transmission episodes.

Prevalence, Concordance, and Transmission of Human Papillomavirus Infection Among Heterosexual Couples in Liuzhou, China: An Observational Perspective Study.

BACKGROUND: Knowledge of human papillomavirus (HPV) transmission dynamics, which have important public health implications for designing HPV vaccination strategies, is scarce in undeveloped areas. METHODS: From May to July 2014, 390 couples were enrolled from the general population in Liuzhou, China. Exfoliated cells from male penis shaft/glans penis/coronary sulcus (PGC) and perianal/anal canal (PA) sites and from female vaginal, vulvar, and PA sites were collected biannually for 1 year. RESULTS: The HPV type-specific concordance rate between couples was 15.5% (95% confidence interval [CI], 8.5%-25.0%). For anogenital HPV transmission, the male-to-female transmission rate (11.5 [95% CI, 4.3-30.7] per 1000 person-months) was similar to the female-to-male transmission rate (11.3 [95% CI, 5.9-21.7] per 1000 person-months). The concordance rates between male PGC site and female vaginal, vulvar, and PA sites were 20.0%, 21.8%, and 14.9%, respectively, which were significantly higher than expected by chance. Infections transmitted from males to females seemed mainly originated from male genital sites, whereas for female-to-male transmission, the vaginal, vulvar, and PA sites might be all involved. CONCLUSIONS: Among the heterosexual couples with relatively conservative sexual behavior, the anogenital HPV transmission rate for females to males is similar to that of males to females. In addition to the vagina and vulva, the female PA site is also an important reservoir for HPV transmission.

Incidence and Clearance of Anal High-risk Human Papillomavirus Infections and Their Determinants Over 5 Years Among Human Immunodeficiency Virus-negative Men Who Have Sex With Men.

BACKGROUND: We aimed to assess the incidence and clearance of anal high-risk human papillomavirus (hrHPV) infections and determinants thereof among human immunodeficiency virus (HIV)-negative men who have sex with men (MSM) over a period of up to 5 years. METHODS: From 2010 to 2015, HIV-negative MSM were followed every 6 months. Anal self-swabs were collected at inclusion and every 6 months thereafter, and were HPV genotyped using the SPF10-PCR DEIA/LiPA25-system-v1. Incidence rates (IRs) and clearance rates (CRs) of incident anal hrHPV infections were assessed by hrHPV type (types 16, 18, 31, 33, 45, 52, and 58). Determinants of transitions between uninfected and infected states were assessed by hrHPV type using a time-homogenous multi-state Markov model. RESULTS: This study included 713 HIV-negative MSM, with a median age of 37 years (interquartile range [IQR] 31-43) and a median number of study visits of 6 (IQR 2-7). The IRs of anal infections had a median of 5.2 per 100 person-years (range: 2.2-7.9) across types, with HPV16 having the highest IR. The CRs of incident anal hrHPV infections had a median of 53.7 per 100 person-years (range: 33.4-65.3) across types, with HPV16 having the lowest CR. Having had over 100 lifetime sex partners was significantly associated with incident anal hrHPV infections in multivariable analyses. CONCLUSIONS: The high incidence and low clearance rates of anal HPV16 infection, compared to other hrHPV types, is consistent with HPV16 being implicated in the large majority of anal cancer cases.

Prevalence of Human Papillomavirus, Human Immunodeficiency Virus, and Other Sexually Transmitted Infections Among Men Who Have Sex With Men in Togo: A National Cross-sectional Survey.

BACKGROUND: Sub-Saharan Africa is a region of both high human immunodeficiency virus (HIV) and anal cancer incidence. We conducted the first national study in Togo to assess human papillomavirus (HPV), HIV, and other sexually transmitted infection (STI) prevalence among men who have sex with men (MSM). METHODS: A multicentric cross-sectional study was conducted among MSM recruited in 4 Togolese cities. Anal swabs were collected to test HPV, herpes simplex virus (HSV), and 7 STIs. RESULTS: Among the 207 MSM, HIV and high-risk HPV (hrHPV) overall prevalence were 26.1% and 44.9%, respectively. The most common hrHPV types were HPV-35 (15.0%) and HPV-16 (13.0%). Prevalence of hrHPV and multiple HPV infections were higher among HIV-infected than among HIV-uninfected MSM (85.2% vs 30.7%, P < 10-5 and 85.2% vs 28.7%, P < 10-5, respectively). Other STIs, except hepatitis B virus, were also more prevalent among HIV-infected MSM (Neisseria gonorrhoeae, P = .03; Mycoplasma genitalium, P = .04; HSV-2, P = .001; and a trend for Chlamydia trachomatis, P = .06). In multivariate analysis (adjusted odds ratio [95% confidence interval]), HIV (10.1 [4.0-25.6]), living in Lomé (2.8 [1.1-7.1]), HSV-2 excretion (26.7 [2.9-244.3]), C. trachomatis (11.7 [2.3-58.9]), and M. genitalium infection (9.6 [3.1-29.9]) were associated with increased risk of hrHPV infection. CONCLUSIONS: We report a high burden of anal STIs with an unusual hrHPV type distribution among MSM, highlighting the critical need of implementation of a national strategy regarding prevention of STIs and vaccination against HPV.

Are associations between HIV and human papillomavirus transmission due to behavioural confounding or biological effects?

OBJECTIVES: Cohort studies have shown significant increased risk of HIV acquisition following human papillomavirus (HPV) detection and increased risk of new HPV detection in individuals with HIV infection, after adjusting for behavioural risk factors. This study uses an individual-based model to assess whether confounding sexual behaviour factors and network level effects can explain these associations between HIV and HPV infection status, without biological interactions. METHODS: The model simulates infection with 13 oncogenic HPV types and HIV. It allows for different relationship types, with heterogeneity in probabilities of concurrency and rates of partner change. No effect of prevalent HPV infection on HIV acquisition is assumed and vice versa. The model is calibrated to South African HIV and type-specific HPV prevalence data using a Bayesian approach. The model is used to simulate cohorts with quarterly HIV and HPV testing from 2000 to 2002. These simulated data are analysed using proportional hazard models. RESULTS: The mean of the unadjusted HRs of HIV acquisition following detection of an oncogenic HPV type calculated for each simulated cohort is 2.6 (95% CI 2.2 to 3.1). The mean of the unadjusted HRs for the effect of HIV on newly detected HPV is 2.5 (95% CI 2.2 to 2.8). Simulated associations between HIV and HPV infection status are similar to corresponding empirical estimates. In sensitivity analyses in which HIV and HPV were assumed to increase each other's transmission risk, simulated associations were stronger but not inconsistent with empirical estimates. CONCLUSIONS: Although we cannot rule out the possibility that associations between HIV and HPV transmission may be due in part to biological interactions, these results suggest that observed associations could be explained entirely by residual confounding by behavioural factors and network-level effects that observational studies cannot account for.