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Human Papilloma virus genotype diversity of anal infection among trans (male to female transvestites, transsexuals or transgender) sex workers in Argentina
Abstract
Reports on the prevalence and genotypes of HPV among trans (male to female transvestites, transsexuals or transgender) sex workers (TSW) are scarce in the literature.
The aim of the study was to determine the infecting HPV genotypes among TSW in Argentina.
119 TSW were recruited. Anal cells were self collected with a cytobrush. HPV DNA detection was carried out by PCR and genotyping was performed by RLB.
HPV prevalence was 97.4%. 103/111 HPV positive samples were genotyped. High risk genotypes were detected in 82.5%. Two or more coinfecting HPV genotypes were found in 70.9%. One case showed up to 10 different coinfecting types. The number of genotypes was not related to condom usage. Infection rates were similar for HIV positive (100%) and HIV negative (95.8%) participants. However, 18.8% of HIV negative had 4-9 different genotypes, while among HIV positive this percentage raised to 46.2% (p=0.006). Prevalence of high risk genotypes and the frequency of each high risk type were similar between HIV positive and HIV negative groups. According to the participants' answers HIV status showed no association with condom usage.
The high HPV prevalence, the coinfection with multiple genotypes and the high frequency of high risk genotypes detected, together with a situation of extreme social marginalization, discrimination and stigmatization make this population to be of extreme vulnerability.
... Included articles captured data from a range of high-income countries. Four or more studies were conducted in the following countries: Argentina [41][42][43][44][45][46], Australia [27,29,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64], Canada [65][66][67][68][69], Hong Kong [70][71][72][73][74][75][76][77], Italy [78][79][80][81], Japan [82][83][84][85][86], Singapore [87][88][89][90], Spain [91][92][93][94][95][96][97][98][99], The Netherlands [100][101][102][103][104][105][106][107] and the USA [108][109][110][111][112][113][114][115]. Two studies were found in each of the following countries: England [116,117], New Zealand [118,119], Portugal [120,121] and Scotland [122,123]. ...
... Sex work legislation varied across the studies, with the largest proportion of studies conducted in countries with partial criminalization [41][42][43][44][45][46][47]62,63,101,102,105,116,117,[119][120][121][122][123][124]127,128]. A summary of the legal status of sex work activity in included studies is described in Table 2 [134]. ...
... Eight studies had all male participants [54][55][56]69,91,111,117,121], whilst a smaller proportion of studies featured both male and female participants [49,66,110,123,129]. Twelve studies included transgender participants [41,43,44,62,63,65,98,106,108,114,118,120], three of which focused solely on transgender sex workers [41,44,108]. The remainder included transgender participants in addition to cisgender male and/or female participants [43,62,63,65,98,106,114,118,120]. ...
There is significant debate regarding the regulation of the sex industry, with a complex range of cultural, political and social factors influencing regulatory models which vary considerably between and within countries. This systematic review examined the available evidence on the relationship between different approaches to sex industry regulation in high-income countries, and associated effects on sex worker health status. Objectives included identification of sex worker health outcomes, including sexual health, substance use and experience of stigma and violence. A search was performed electronically in eight scholarly databases which yielded 95 articles which met the criteria for inclusion. Findings suggested that sex workers in legalised and decriminalized countries demonstrated greater health outcomes, including awareness of health conditions and risk factors.
... 7,8 Previous studies among transgender women show high rates of HPV infection and HPV-related disease and estimated prevalence ranges from 40% to 97.4%. [9][10][11] In addition, research has shown high rates of STIs and behaviors associated with sex work, such as unprotected receptive anal intercourse significantly increases risk for anal HPV and HIV 12 and anal sex is common in many populations. 13 Specifically, among transgender women there may be a heightened risk for HPV infection 14 due to a possible higher frequency of HIV infection, forced sex, and exchange of sex for money, food, shelter, or drugs. ...
... 25 Few cross-sectional studies have focused on anal HPV infection or HPV-associated disease among transgender populations, with very small samples or where data are not presented separately (transgender women are included in the men who have sex with men category). [9][10][11]14 It has been noted that studies in this population often do not report or disaggregate data by sex work history (SW) 26 and the lack of data complicates our understanding of how to address prevention of HPV-related diseases among transgender women. ...
... High hrHPV prevalence is generally consistent with data reported by other authors, although most previous studies did not stratify by sex work. 10,31 For example, one of the first studies among adult transgender women unvaccinated against HPV, which evaluated the prevalence of anal HPV, done in Argentina and which only included sex workers, 10 reported that the presence of any HPV type was 97.4% and for oncogenic types was 82.5%, prevalence levels quite a bit higher ...
Purpose: The prevalence of high-risk human papillomavirus (hrHPV) infection among transgender women has been reported to be very high and sexually transmitted infection (STI) prevention strategies have focused on transgender women who engage in sex work. The purpose of our study was to describe hrHPV infection prevalence among a group of transgender women and to explore the differences according to sex work history (SW). Methods: The Condesa Study, an HPV vaccine, and screening study, recruited 207 transgender women without previous HPV vaccination, ages 18-60, from two clinics in Mexico City that provide HIV and transgender health care (May 2018-December 2019). At enrollment, they completed a questionnaire on sociodemographic and sexual behavior data. The hrHPV DNA genotyping was done on self-collected anal samples. Factors associated with hrHPV, stratified by presence or absence of SW, were assessed with multiple logistic regression. Results: A total of 43.5% of participants reported a history of SW. Anal hrHPV prevalence was 62.0% among participants with a history of SW and 52.0% among those without. Overall, 1 in 4 (26.6%) participants were living with HIV. Independent risk factors associated with hrHPV among transgender women with a history of SW were younger age, younger age at first anal intercourse (15-17 years), and greater number of sexual partners in the last 3 months. Among transgender women who had not done SW, greater number of sexual partners in the last 3 months and self-reported STIs were associated with hrHPV. Conclusions: Prevalence of anal infection with hrHPV was high among transgender women. Our results support that other sexual behaviors different from participating in SW contribute to the high prevalence of HPV and that there is an urgent need to include all transgender women in prevention programs for HPV and associated cancers, regardless of SW.
... For HPV, PCR using GP5+ and biotin-labeled GP6+ generic HPV primers was performed to amplify 140 bp in the L1 viral región. GP-PCR positive samples were typed by reverse line blot hybridization using 6,11,16,18,26,31,33,34,35,39,40,42,43,44,45,51,52,53,54,55,56,57,58,59,61,66,68,70,71,72,73,81,82,83,84 and CP6108 type-specific oligoprobes. Positive reactions were revealed by chemiluminescence using AmershamTM ECLTM Detection Reagents according to manufacturer recommendations (GE Healthcare, Little Chalfont, UK). ...
... This study reports C trachomatis infection prevalence among MSM for the first time in Argentina. The 2.9% prevalence of C trachomatis anal infection detected among MM group is higher than that observed in STI symptomatic adult patients (1.85%) [39], but lower than that detected among male-to-female transvestite sex workers (TSWs) (5.0%) [40]. Although C trachomatis infection is less prevalent than the other STIs tested here, it is essential that the prevalence of this infection be monitored, as studies have reported increasing rates of infection among MSM. ...
... The high prevalence of HPV infection detected in our study is consistent that from a recent study in Argentina among TSWs which found an HPV prevalence of 97.4% [40]. The results presented here are also similar to those from other countries, which found HPV prevalence around 90-96% in HIV positive individuals and from 40 to 60% among HIV negative MSM [12,14,41]. ...
The aim of this study was to estimate the prevalence of HIV and other STIs, among MSM from Buenos Aires (2007-2009).
Responding Driven Sampling was used for recruitment of MSM. Participants completed a structured web-based survey and provided biological samples.
A total of 496 MSM were studied for HIV, HBV, HCV, and T. pallidum infections. Chlamydia and HPV diagnoses were only performed in 98 and 109 participants, respectively. Prevalence of HIV was 17.3%, HBV 22.9%, HCV 7.5%, T. pallidum 20.5%, HPV 83.5%, and C. trachomatis 1.7%. In the year prior to the evaluation, 71% of the participants had had sex with men and/or trans and women (MMW) while 29% had not had sex with women (MM). Comparing MM to MMW, prevalence of HIV (30.7% vs. 11.9%, p<0.001), HBV (36.4% vs. 17.8%, p<0.001), T. pallidum (32.1% vs. 15.7%, p<0.001), and HPV (88.3% vs. 70.4%, p = 0.039) were significantly higher among MM, whereas no significant differences were found for HCV and C. trachomatis. The MM group had also significantly higher HIV incidence (5.60 vs. 4.28 per 100 persons-year, p = 0.032). HPV genotypes 16, 6, and 11 were the most frequently found; 40.7% of the MSM had more than one genotype and one high risk genotype was detected in 43.6% of participants.
Both MM and MMW are at high risk of infection for HIV and other STIs. Rates of HIV, HBV, T. pallidum and HPV infections are higher in the MM group.
... The performance of anal sexual practice (insertive and receptive) and ejaculation in the mouth without a condom and how the feminization of transsexual women can influence the use or not of the condom were identified. It was also possible to evidence high prevalence values of HIV, Hepatitis B and syphilis, in addition to the high-risk genotypes of HPV 9,13,26,[29][30][33][34][35][36][37]41,43,[45][46][47]53 . ...
... The risks of illness in the exposure of sex work are recognized due to the social conditions imposed by violence, prostitution, and use of drugs and alcohol 50 . It was possible to identify how the negotiation of the sex work prices aiming at sexual practices without a condom, in addition to the fulfillment of sexual desires related to fetishization of the body and the exploitation of people considered abject 39 , result in sexual commercialization associated with physical and psychological aggression to the detriment of health and lives that "do not matter" 7,30,41 . ...
Objective:
to identify the health vulnerabilities of transgender sex workers.
Method:
an integrative review conducted in July 2020 in the PubMed, Web of Science, SCOPUS, CINAHL, IBECS and LILACS databases, with no language or time restrictions. The following descriptors indexed in DeCS and MESH and their respective synonyms were used: “Transgender persons”, “Sex workers” and “Health vulnerability”. The data were analyzed based on thematic analysis.
Results:
a total of 547 articles were retrieved and, after the selection and analysis process, 34 were included in this review. Four thematic classes emerged: “Knowledge, prevention and exposure to STIs in sex work”; “Use (and abuse) of illegal substances and alcohol”; “The social and structural dimension of vulnerabilities: from weakened support networks to violence reproduced against dissident bodies”; and “Psychosocial diseases, discrimination and challenges of transgender sex workers”.
Conclusion:
the health vulnerabilities experienced by transgender sex workers are marked by discrimination, social exclusion, stigma, incarceration contexts, physical, psychological and sexual violence and use of illegal substances and alcohol, in addition to difficulties in accessing essential services such as health, education and leisure.
... For example, a study of 111 transgender sex workers in Argentina found HPV DNA in 97% of anal mucosa samples. Highrisk carcinogenic genotypes were detected in 83% of the participants, and 71% were coinfected with 2 or more HPV genotypes (23). In another study conducted among transwomen in Lima, Peru, visible anogenital warts were detected in 22% of the participants (24). ...
Transgender people comprise a diverse group of individuals whose gender identity or expression differs from that originally assigned to them at birth. Some, but not all, transgender people elect to undergo medical gender affirmation, which may include therapy with cross-sex hormones and/or surgical change of the genitalia and other sex characteristics. As cross-sex hormones administered for the purposes of gender affirmation may be delivered at high doses and over a period of decades, the carcinogenicity of hormonal therapy in transgender people is an area of considerable concern. In addition, concerns about cancer risk in transgender patients have been linked to sexually transmitted infections, increased exposure to well-known risk factors such as smoking and alcohol use, and the lack of adequate access to screening. Several publications have identified cancer as an important priority in transgender health research and called for large-scale studies. The goals of this article are to summarize the evidence on factors that may differentially affect cancer risk in transgender people, assess the relevant cancer surveillance and epidemiologic data available to date, and offer an overview of possible methodological considerations for future studies investigating cancer incidence and mortality in this population.
... 24,25 Among the studies of anal HPV prevalence in HIV-negative individuals, twice as many report data among men 17,26-36 than among women. [37][38][39][40][41][42] Anal HPV studies among transgendered persons are rare, 43 and we are aware of no studies among women who have sex with women (MSW). ...
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. © 2014 Wiley Periodicals, Inc.
Objectives
Sexual gender minority (SGM) populations are at risk for human papillomavirus (HPV)–related cancers of the anogenital tract and oropharynx and often face barriers to health care. The goals of this document are to clarify language to provide inclusive care for SGM populations and to provide recommendations for screening and prevention of HPV-related cancers in SGM populations.
Materials and Methods
An expert committee convened by the American Society for Colposcopy and Cervical Pathology performed a narrative review of the literature through February 2023. A comprehensive MEDLINE database search was performed for relevant studies. The literature review was divided into categories by organ/topic and by SGM population. Given the variability in available data for several of the categories, recommendations were made based on national guidelines where appropriate or expert opinion where there were less data to support risk-based guidelines.
Results
Definitions and terminology relevant to SGM populations are presented. The authors advocate the adoption of sexual orientation gender identity data collection and an organ-based screening approach, which is possible with knowledge of patient anatomy, sexual behaviors, and clinical history. This includes screening for cervical cancer per national recommendations, as well as screening for anal, vulvar, vaginal, penile, and oral cancers based on risk factors and shared clinical decision making. The authors recommend consideration of HPV vaccination in all SGM individuals up to age 45 years old who are at risk.
Conclusions
An organ-based screening approach is part of a global strategy to create an inclusive care environment and mitigate barriers to screening and prevention of HPV-mediated cancers in SGM populations.
Objective:
The aim of the study was to assess risk factors for anal human papillomavirus (HPV) infection and anal dysplasia among a cohort of transgender women (TGW).
Methods:
A retrospective chart review was conducted based on electronic medical records of TGW patients seen in the University of Miami Health System between 2010 and 2016. Outcome measures included risk factors of anal dysplasia, including HIV infection, receptive anal intercourse, and smoking history. Descriptive statistical analysis and χ testing were used.
Results:
Sixty-nine TGW patients' charts were reviewed. Patients' ages ranged from 18 to 72 (mean = 38 [15]). Twenty-two (30%) were older than 50 years; 10 (15%) were black/African descent; 20 (29%) reported a smoking history; 6 (9%) were HIV positive, and 28 (72%) among those with known partner preference (n = 39) reported male partners. Male partner preference was significantly associated with being black/African descent (p = .009) and being single (p = .048). Older age was significantly associated with HIV-positive status (p = .023). The average number of risk factors per person was 2.10 (0.97). Sixty-one years or older had the highest average number of risk factors (2.90 [0.88]).
Conclusions:
Because rates of HIV, dangerous sexual behaviors, and other risk factors for anal dysplasia continue to persist among TGW, this study reinforces the need to increase the focus on anal health in the care of TGW and the need for further research to guide patient care and anal dysplasia screening strategies among those individuals.
Experiences of cancer among trans people is a neglected area of study and requires greater time and resources in order to provide them better care. Trans people’s experience with cancer is greatly influenced by their own experiences of discrimination in society and health care. In addition, the use of exogenous hormones could influence the production of various cancers. This chapter will outline the many factors that can impact the production of cancer and how social factors can affect trans people’s ability to seek treatment and recover. The chapter will also identify important recommendations that would benefit trans people in identifying and treating cancer. Overall, greater attention is needed on chronic health issues like cancer. Clearly, more research is needed in understanding the findings within many case studies of trans people and cancer. Health professionals will also need greater education in order to build up their cultural competency in treating trans people.
Detectable human papillomavirus (HPV) DNA is the most common sexually transmitted infection. Reports on the prevalence of detectable HPV DNA among transsexuals (not sex workers) are scarce. The objective of the study was to determine the prevalence of detectable HPV DNA in a clinic sample of transsexuals and to assess the relationship between detectable HPV DNA and cytological outcomes.
Clinical samples (oral, anal, vaginal, cervicovaginal and penile scraped cells) from 35 transsexuals (surgically treated and surgically untreated) who attended the outpatient Clinic of Gender Identity Dysphoria of the Department of Obstetrics and Gynecology of Policlinico Hospital (Bari, Italy) were collected for cytological analysis and HPV DNA detection and typing. All enrolled subjects answered an anonymous structured questionnaire about their sexual habits. Serological status for other sexually transmitted diseases (hepatitis B virus (HBV), hepatitis C virus (HCV), HIV and syphilis) was also evaluated.
HPV DNA was detected in 14 of 35 patients (40.0%). The prevalence of detectable HPV DNA was 38.2% (13/34) in tested anal samples, 9.1% (2/22) in vaginal samples and 8.3% (1/12) in penile samples. Oncogenic HPV genotypes have been detected in 93% of HPV-positive transsexuals. More than one-third (35.7%) of HPV-positive transsexuals were infected with at least one of the four vaccine-preventable genotypes, 6, 11, 16 and 18.
The high rate of detectable HPV DNA by oncogenic types suggests that periodic cytological screening and clinical evaluation may be necessary since transsexuals are at high risk of anogenital cancer. Also promoting HPV vaccination in younger subjects may be advisable.
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Due to the scarce data on the prevalence of sexually transmitted infections (STIs) among male-to-female trans-sex workers (TSW) and male sex workers (MSW) in Argentina, the present study aimed to estimate the incidence of human immunodeficiency virus (HIV), and the prevalence of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and Treponema pallidum. Human papillomavirus (HPV) and Chlamydia trachomatis infections were tested among TSW.
Two hundred and seventy-three TSW and 114 MSW were recruited by nongovernmental organizations. HIV incidence was estimated by STARHS (serologic testing algorithm for recent HIV seroconversion). HPV and C. trachomatis infections were tested in anal cells from TSW.
TSW showed significantly higher prevalences of HIV (34.1 vs. 11.4%), HBV (40.2 vs. 22.0%), and T. pallidum (50.4 vs. 20.4%) than MSW. TSW tested positive for HPV in 111/114 cases and for C. trachomatis in 4/80 cases. Investigation of HBV, HCV, HIV, and T. pallidum co-infections showed that 72% of TSW and 39% of MSW had at least one STI. T. pallidum was the most frequent mono-infection. The estimated HIV incidence was 10.7 per 100 person-years (95% confidence interval (CI) 3.8-17.7) for TSW and 2.3 per 100 person-years (95% CI 0-6.7) for MSW.
The high prevalence of STIs and the high incidence of HIV demonstrate the great vulnerability of these high-risk populations and indicate the urgent need for preventive strategies on intervention and facilitation of access to healthcare programs.
Infection with human papilloma virus (HPV) is the main cause of cervical cancer, but the risk associated with the various HPV types has not been adequately assessed.
We pooled data from 11 case-control studies from nine countries involving 1918 women with histologically confirmed squamous-cell cervical cancer and 1928 control women. A common protocol and questionnaire were used. Information on risk factors was obtained by personal interviews, and cervical cells were collected for detection of HPV DNA and typing in a central laboratory by polymerase-chain-reaction-based assays (with MY09/MY11 and GP5+/6+ primers).
HPV DNA was detected in 1739 of the 1918 patients with cervical cancer (90.7 percent) and in 259 of the 1928 control women (13.4 percent). With the GP5+/6+ primer, HPV DNA was detected in 96.6 percent of the patients and 15.6 percent of the controls. The most common HPV types in patients, in descending order of frequency, were types 16, 18, 45, 31, 33, 52, 58, and 35. Among control women, types 16, 18, 45, 31, 6, 58, 35, and 33 were the most common. For studies using the GP5+/6+ primer, the pooled odds ratio for cervical cancer associated with the presence of any HPV was 158.2 (95 percent confidence interval, 113.4 to 220.6). The odds ratios were over 45 for the most common and least common HPV types. Fifteen HPV types were classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82); 3 were classified as probable high-risk types (26, 53, and 66); and 12 were classified as low-risk types (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108). There was good agreement between our epidemiologic classification and the classification based on phylogenetic grouping.
In addition to HPV types 16 and 18, types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 should be considered carcinogenic, or high-risk, types, and types 26, 53, and 66 should be considered probably carcinogenic.
Due to the scarce data on the prevalence of sexually transmitted infections (STIs) among male-to-female trans-sex workers (TSW) and male sex workers (MSW) in Argentina, the present study aimed to estimate the incidence of human immunodeficiency virus (HIV), and the prevalence of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and Treponema pallidum. Human papillomavirus (HPV) and Chlamydia trachomatis infections were tested among TSW.
Two hundred and seventy-three TSW and 114 MSW were recruited by nongovernmental organizations. HIV incidence was estimated by STARHS (serologic testing algorithm for recent HIV seroconversion). HPV and C. trachomatis infections were tested in anal cells from TSW.
TSW showed significantly higher prevalences of HIV (34.1 vs. 11.4%), HBV (40.2 vs. 22.0%), and T. pallidum (50.4 vs. 20.4%) than MSW. TSW tested positive for HPV in 111/114 cases and for C. trachomatis in 4/80 cases. Investigation of HBV, HCV, HIV, and T. pallidum co-infections showed that 72% of TSW and 39% of MSW had at least one STI. T. pallidum was the most frequent mono-infection. The estimated HIV incidence was 10.7 per 100 person-years (95% confidence interval (CI) 3.8-17.7) for TSW and 2.3 per 100 person-years (95% CI 0-6.7) for MSW.
The high prevalence of STIs and the high incidence of HIV demonstrate the great vulnerability of these high-risk populations and indicate the urgent need for preventive strategies on intervention and facilitation of access to healthcare programs.
There is a paucity of data on whether or not women can be reinfected with human papillomavirus (HPV) types to which they were exposed to earlier in life and on the role of natural immunity. The observation of HPV infection at older ages may be explained by the reactivation of a latent infection or new exposure from sexual activity. Our objective was to analyze the association between reinfection and sexual activity. We analyzed data from 2,462 women enrolled in the Ludwig-McGill cohort and followed every 4 to 6 months for up to 10 years. We performed HPV typing and viral load measurements via PCR and determined HPV-16 seroreactivity at enrollment. Incidence of infection and reinfection were estimated for individual types. Adjusted relative risks (RR) for the association between infection/reinfection and new sexual partners were calculated using Cox regression. Rates of initial infection and reinfection postclearance were statistically comparable. RRs of initial infection or reinfection were consistently associated with new sexual partners [2.4 (95% confidence intervals; 95% CI, 2.0-3.1) for first infection, 3.7 (1.1-13.8) for reinfection with the same type, and 2.3 (1.5-3.7) for reinfection with a different type]. Reinfection in older women was also associated with new sexual partners (RR, 2.8; 95% CI, 1.4-5.3) as were new infections with HPV-16 among women with serologic evidence of prior HPV-16 exposure (RR, 3.0; 95% CI, 1.6-5.3). Viral loads at initial infection and at reinfection were comparable. HPV infection and reinfection were strongly associated with sexual activity. This study suggests that natural immunity does not play a role in controlling the extent of reinfections.
Infection with high-risk human papillomavirus (HPV) is the main cause of high-grade cervical intraepithelial neoplasia (CIN) and cancer. It has been suggested that information about high-risk HPV type-specific infection might make cervical cancer screening more effective. Persistent HPV infection could also be a useful screening marker. We estimated the long-term risk of high-grade CIN after one-time detection of high-risk HPV DNA and after persistent infection with individual high-risk HPV types.
A cohort of 8656 women from the general population of Denmark was examined twice, 2 years apart (first study examination: May 15, 1991, to January 31, 1993; second study examination: October 1, 1993, to January 31, 1995). The women underwent a gynecological examination and cervical cytology and had swabs taken for HPV DNA analysis by the Hybrid Capture 2 and line probe assays. The women were followed up through the nationwide Danish Pathology Data Bank for cervical neoplasia for up to 13.4 years. The absolute risk of developing cervical lesions before a given time was estimated as a function of time.
For women with normal cytological findings who were concurrently HPV16 DNA positive at the second examination, the estimated probability of developing CIN grade 3 (CIN3) or worse within 12 years of follow-up was 26.7% (95% confidence interval [CI] = 21.1% to 31.8%). The corresponding risks among those infected with HPV18 was 19.1% (95% CI = 10.4% to 27.3%), with HPV31 was 14.3% (95% CI = 9.1% to 19.4%), and with HPV33 was 14.9% (95% CI = 7.9% to 21.1%). The absolute risk of CIN3 or worse after infection with high-risk HPV types other than HPV16, HPV18, HPV31, or HPV33 was 6.0% (95% CI = 3.8% to 8.3%). The estimated absolute risk for CIN3 or cancer within 12 years of the second examination among women who were HPV16 DNA positive at both examinations was 47.4% (95% CI = 34.9% to 57.5%); by contrast, the risk of CIN3 or worse following a negative Hybrid Capture 2 test was 3.0% (95% CI = 2.5% to 3.5%).
HPV16, HPV18, HPV31, and HPV33 infection and especially HPV16 persistence were associated with high absolute risks for progression to high-grade cervical lesions. The results indicate the potential value of genotyping in cervical cancer screening. Given that HPV DNA-negative women retained their low risk of CIN3 or worse for many years, frequent screening of these women may be unnecessary.
The incidence of human papillomavirus (HPV)-associated anal cancer in men who have sex with men (MSM) is striking and has not been mitigated by the use of highly active antiretroviral therapy. Detection and treatment of high-grade anal intraepithelial neoplasia (HGAIN) may reduce the incidence of anal cancer. Anal cytology is a useful tool to detect HGAIN; annual screening of HIV-positive MSM and biennial screening of HIV-negative MSM appears to be cost-effective. MSM with abnormal cytology should be referred for high-resolution anoscopy and biopsy. Individuals with HGAIN should receive treatment; treatment modalities for HGAIN demonstrate moderate efficacy and are usually well tolerated, but greater study is required to determine which treatment is optimal. Large prospective studies are needed to document the efficacy of screening and treatment of HGAIN on anal cancer incidence. The HPV vaccine holds promise for primary prevention of anal cancer in MSM, but significant implementation challenges remain.
To determine the prevalence and risk factors for anal human papillomavirus (HPV) infection in community-based cohorts of homosexual men in Sydney, Australia.
A cross-sectional study in consecutively presenting participants in the positive Health and Health in Men cohorts in 2005. HPV testing was performed on anal PreservCyt specimens collected from 316 homosexual men (193 HIV-negative, 123 HIV-positive) using the Digene Hybrid Capture 2 (HC-2) assay for detection of low-risk (LR) and high-risk (HR) genotypes. HPV genotype testing was also performed on a subset of 133 men (93 HIV-negative, 36 HIV-positive) using Roche Linear Array (LA) assay.
HC-2 detected HPV infection in 79% of men (LR 55%, HR 69%). HIV-positive men were more likely than HIV-negative men to have LR-HPV (OR 3.5, 95% CI 2.1 to 5.7) and HR-HPV (OR 5.5, 95% CI 3.0 to 10.2). LA detected HPV infection in 95% of men (LR 85%, HR 77%). HIV-positive men had a mean of 7.1 HPV types compared to 4.2 in HIV-negative men; the difference was significant for both LR-HPV (p<0.001) and HR-HPV (p<0.001). HPV-16 was detected in 36% of HIV-positive and 27% of HIV-negative men. There was no consistent trend in HPV prevalence with increasing age. HR-HPV detection was associated with anal bleeding for HIV-positive men and anal warts for HIV-negative men.
Anal HPV infection was nearly universal in this community-based sample of homosexual men. A wide variety of HPV genotypes were detected, and co-infection with multiple genotypes was common. Anal HPV infection is more prevalent and more diverse in HIV-positive than HIV-negative homosexual men.
In this study, we developed a simple and fast typing procedure for 37 mucosotropic human papillomavirus (HPV) types using a nonradioactive reverse line blotting (RLB) procedure for general primer (GP5+/6+) PCR products. This system has the advantages not only that in a simple format, up to 42 PCR products can be simultaneously typed per membrane per day, but also that after stripping, the membranes can be easily rehybridized at least 15 times without a loss of signal. RLB appeared highly specific, and its sensitivity was identical to that of conventional typing performed with type-specific oligonucleotide probes in an enzyme immunoassay (EIA). The performance of RLB typing was evaluated with samples of HPV-positive cervical scrapings (n = 196) and biopsies of cervical premalignant lesions (n = 100). The distribution of HPV genotypes detected in these samples was in line with the distribution expected on the basis of literature data. In addition, RLB and EIA typing procedures were compared for the typing of high-risk HPV types in GP5+/6+ PCR products of 210 cervical scrapings from high-risk HPV-positive women who participated in a population-based screening program. The typing procedures had an excellent overall agreement rate of 96.5% (kappa value, 0.77). RLB was successful in detecting multiple HPV infections as well as single infections. In conclusion, the GP5+/6+ PCR-RLB procedure appeared to be a reliable and simple approach that may be of great value for large epidemiological studies, population-based cervical cancer screening programs, and vaccination trials that require high-throughput HPV typing.
In the United States, anal cancer in men who have sex with men (MSM) is more common than cervical cancer in women. Human papillomavirus (HPV) is causally linked to the development of anal and cervical cancer. In women, cervical HPV infection peaks early and decreases after the age of 30. Little is known about the age-specific prevalence of anal HPV infection in human immunodeficiency virus (HIV)-negative MSM.
We studied the prevalence and determinants of anal HPV infection in 1218 HIV-negative MSM, 18-89 years old, who were recruited from 4 US cities. We assessed anal HPV infection status by polymerase chain reaction.
HPV DNA was found in the anal canal of 57% of study participants. The prevalence of anal HPV infection did not change with age or geographic location. Anal HPV infection was independently associated with receptive anal intercourse (odds ratio [OR], 2.0; P<.0001) during the preceding 6 months and with >5 sex partners during the preceding 6 months (OR, 1.5; P<.0001).
Urban, HIV-negative MSM have a stable, high prevalence of anal HPV infection across all age groups. These results differ substantially from the epidemiologic profile of cervical HPV infection in women. This may reflect differences between these populations with respect to the number of new sex partners after the age of 30 and may explain the high incidence of anal cancer in MSM.
Human papillomavirus (HPV) is sexually transmitted and causes cervical cancer. Although HPV can infect men and women, little is known about infection in men. Specifically, the prevalence of type-specific HPV infection and the distribution of infections by anogenital anatomic site in men are incompletely characterized.
We tested 463 men ages 18 to 40 years for HPV at the glans/corona, penile shaft, scrotum, urethra, perianal area, anal canal, and in a semen sample. Eligible men acknowledged no history of genital warts and had sexual intercourse with a woman within the past year. HPV testing by PCR and reverse line blot genotyping for 37 types was conducted on each of the specimens from the seven sampling sites.
When HPV results from any sampling site were considered, 237 (51.2%) men were positive for at least one oncogenic or nononcogenic HPV type, and another 66 (14.3%) men were positive for an unclassified HPV type. The types with the highest prevalence were HPV-16 (11.4%) and 84 (10.6%). External genital samples (glans/corona, shaft, and scrotum) were more likely than anal samples to contain oncogenic HPV (25.1% versus 5.0%). HPV-positive penile shaft and glans/corona samples were also more likely to be infected with multiple HPV types than other sites.
More complete anogenital sampling and sensitive detection for 37 HPV types resulted in a higher HPV prevalence in primarily asymptomatic men than reported previously. The penile shaft was the site most likely to be HPV positive and harbored the greatest proportion of multiple type and oncogenic infections. These results have implications for research of HPV among men and transmission between partners.
The most common cause of mortality related to human papillomavirus (HPV) infection is cervical cancer. However, male HPV infection is also an important concern, both for the disease burden in men and for the risk of transmission to women. HPV is associated with a variety of cancers in men, including anal cancer and a subset of penile and oral cancers. The incidence of anal and oral cancers related to HPV is increasing in the general population and is growing even faster among individuals who are immunocompromised because of human immunodeficiency virus (HIV) infection. Penile HPV infection is very common among heterosexual men and remains high throughout a wide range of ages. Likewise, anal HPV infection and anal intraepithelial neoplasia are very common throughout a wide range of ages in both HIV-negative and HIV-positive men who have sex with men. Other HPV-related diseases of clinical importance in men include condylomata acuminata (genital warts) and recurrent respiratory papillomatosis. The quadrivalent HPV vaccine has been shown to be highly efficacious in the prevention of genital warts in women and precancerous lesions of the cervix, vulva, and vagina. In addition, recent interim data have shown that the quadrivalent HPV vaccine is highly effective in reducing external genital lesions in young men. Although the protective efficacy of HPV vaccination in men has not yet been fully established-pending the outcome of public policy discussions and cost-efficacy studies-there may be a strong rationale for vaccinating boys, similar to girls, at an early age when they have had limited or no prior sexual activity.
A vaccine targeting human papillomavirus (HPV) types 16 and 18, which are associated with 80% of anal cancers, is efficacious in men. High-risk populations such as men who have sex with men (MSM) might especially benefit from vaccination. I aimed to estimate the cost-effectiveness of HPV vaccination of MSM in the USA.
I constructed decision-analytic models to estimate the direct health and economic outcomes of HPV vaccination (against types 6, 11, 16, and 18) for prevention of HPV-related anal cancer and genital warts. The model parameters that were varied were age at vaccination (12 years, 20 years, and 26 years), previous exposure to vaccine-targeted HPV types, and prevalence of HIV-1. I used the models to conduct sensitivity analyses, including duration of vaccine protection, vaccine cost, and burden of anal cancer and genital warts.
In a scenario of HPV vaccination of MSM at 12 years of age without previous exposure to HPV, compared with no vaccination, vaccination cost US$15,290 per quality-adjusted life-year gained. In scenarios where MSM are vaccinated at 20 years or 26 years of age, after exposure to HPV infections, the cost-effectiveness ratios worsened, but were less than $50,000 per quality-adjusted life-year under most scenarios. For example, HPV vaccination of MSM at 26 years cost $37,830 per quality-adjusted life-year when previous exposure to all vaccine-targeted HPV types was assumed to be 50%. Outcomes were most sensitive to variations in anal cancer incidence, duration of vaccine protection, and HIV prevalence in MSM.
HPV vaccination of MSM is likely to be a cost-effective intervention for the prevention of genital warts and anal cancer.
US National Cancer Institute.
Human papillomavirus (HPV) is a common sexually transmitted agent that causes anogenital cancer and precancer lesions that have an inflammatory infiltrate, may be friable and bleed. Our aim was to determine the association between anal HPV infection and HIV acquisition.
A prospective cohort study.
We recruited 1409 HIV-negative men who have sex with men from a community-based setting in Boston, Denver, New York and San Francisco. We used Cox proportional hazards regression modeling and assessed the independent association of HPV infection with the rate of acquisition of HIV infection.
Of 1409 participants contributing 4375 person-years of follow-up, 51 HIV-seroconverted. The median number of HPV types in HPV-infected HIV-seroconverters was 2 (interquartile range 1-3) at the time of HIV seroconversion. After adjustment for sexual activity, substance use, occurrence of other sexually transmitted infections and demographic variables, there was evidence (P = 0.002) for the effect of infection with at least two HPV types (hazard ratio 3.5, 95% confidence interval 1.2-10.6) in HIV seroconversion.
Anal HPV infection is independently associated with HIV acquisition. Studies that incorporate high-resolution anoscopy to more accurately identify HPV-associated disease are needed to determine the relationship between HPV-associated disease and HIV seroconversion.
Persistent human papillomavirus (HPV) infection is very frequent in HIV-positive men who have sex with men. This review summarizes recent data on papillomavirus-induced anal intraepithelial neoplasia and anal cancer in these patients. Moreover, data are provided on penile and oral HPV-associated diseases, for which only limited information is available in the literature.
The incidence of anal intraepithelial neoplasia rises in HIV-positive men who have sex with men despite the introduction of highly active antiretroviral therapy. Increasing evidence indicates that high-grade lesions can progress to anal cancer over time. Anal cytology has been recommended as the primary screening tool for anal dysplasia in the at-risk population. Individuals with abnormal cytology should undergo high-resolution anoscopy to appropriately identify and treat dysplastic lesions. Anal cancer has become one of the most common non-AIDS-defining tumors in HIV-infected individuals. In the era of highly active antiretroviral therapy, the outcome of combined chemoradiotherapy in HIV-positive individuals with anal cancer is similar to that in HIV-negative persons. Penile and oral HPV-associated diseases seem to be more frequent in HIV-positive men than reported for HIV-negative heterosexual men.
Diagnostic and therapeutic guidelines should be implemented for at-risk populations for anal dysplasia/anal cancer, such as HIV-positive men who have sex with men. More study is required to get better insights into the natural history of penile and oral HPV-associated benign and malignant lesions.
Human papillomavirus (HPV) causes anal intraepithelial neoplasia (AIN) in HIV-seropositive men. The detection of HPV genotypes in anal biopsies and swabs was compared.
HPV DNA was detected in anal swabs and biopsies obtained concurrently from 154 HIV-seropositive men [31 without AIN, 60 low-grade AIN (AIN-1), 62 high-grade AIN (AIN-2,3), and 1 indeterminate AIN] under or eligible to highly active antiretroviral therapy.
HPV DNA was detected in 24.2% of normal biopsies compared with 93.5% with AIN-2,3 (P < 0.001) and 88.3% with AIN-1 (P < 0.001). The proportion of biopsies containing multiple genotypes was greater in AIN-1 (n = 21, 35.0%; P = 0.002) and AIN-2,3 (n = 38, 58%; P < 0.001) than in normal biopsies (n = 2, 6.5%). The most frequent genotypes in order of frequency were in AIN-2,3 biopsies HPV-16, 18, 58, and 45 and were in AIN-1 biopsies HPV-6, 11, 16, and 39. Controlling for age, CD4 count, and smoking, the presence of high-risk HPV DNA in biopsies [odds ratio (OR) = 50.8, 95% confidence interval (CI): 13.0 to 199.5] but not in swabs (OR = 2.0, 95% CI: 0.6 to 7.0) was associated with AIN-2,3.
AIN-2,3 was associated with high-risk HPV infection detected in biopsies but not in swabs in men under or starting highly active antiretroviral therapy, possibly due to the presence of HPV foci outside of the neoplastic lesion.
Acquisition and clearance of cervical human papillomavirus (HPV) infection were analyzed among 1425 low-income women attending
a maternal and child health program in São Paulo, Brazil. Specimens collected every 4 months were tested by a polymerase chain
reaction protocol (MY09/11). In all, 357 subjects were positive at least once. There were 1.3% new infections per month, with
38% cumulative positivity after 18 months. Of 177 positive subjects at enrollment, only 35% remained infected after 12 months.
The monthly clearance rate was higher for nononcogenic types (12.2%; 95% confidence interval [CI], 9.6–15.4) than for oncogenic
HPV infections (9.5%; 95% CI, 7.5–11.9). Median retention times were 8.1 months (95% CI, 7.8–8.3) for oncogenic types and
4.8 months (95% CI, 3.9–5.6) for nononcogenic HPV infections. The mean infection durations were 8.2 and 13.5 months for nononcogenic
and oncogenic types, respectively. Although a woman's age did not affect mean duration for oncogenic types (13–14 months),
nononcogenic-type infections lasted longer (10.2 months) among younger (<35 years old) than in older women (5.6 months).
To develop strategies for prevention and early treatment of human papillomavirus (HPV) anal and penile cancer, a better understanding of related sexual behavior risk factors is needed.
The goal of this study was to establish the prevalence of anal and coronal sulcus HPV in a group of men who have sex with men participating in a Dutch gay-cohort study, to identify risk factors associated with HPV infection in this group, and to investigate the presence of identical HPV types in couples with stable relationships.
A cross-sectional study of 241 HIV-negative and 17 HIV-positive men who have sex with men visiting the sexually transmitted disease clinic of the Erasmus MC for a regular and scheduled examination. Participants underwent a routine venereological examination including HIV serologic analysis, and swabs were taken from the coronal sulcus and anus for HPV DNA testing. All subjects were asked to complete a questionnaire on sexual risk behavior.
HPV DNA was detected at the coronal sulcus in 23.5% of the HIV-positive men and in 15.8% of the HIV-negative men (P=0.492). In anal specimens, HPV DNA was detected in 64.7% of the HIV-positive men and 32.8% of the HIV-negative men (P=0.015). High-risk HPV types (P=0.007) and 2 or more different HPV genotypes (P=0.006) were seen more often in anal specimens of HIV-positive persons than in specimens of HIV-negative persons. A factor possibly associated with the presence of anal HPV infection was a concomitant anal infection with Chlamydia trachomatis, gonococci, or herpes simplex virus (P=0.059). In only 16.7% of HPV-positive steady couples, both companions showed the presence of one or more identical HPV genotypes.
In this study, anal HPV DNA was detected more often than HPV DNA at the coronal sulcus. HIV positivity was associated with a higher prevalence of high-risk, but not with low-risk HPV types, at the anus. No association was found between HIV positivity and presence of high-risk HPV at the coronal sulcus. No sexual behavioral determinants for the presence of HPV could be identified. Concomitant anal infection with C trachomatis, gonococci, or herpes simplex virus may be associated with HPV infection. In the majority of steady couples, partners were infected with different HPV types.
Preparing for HPV vaccine programs, studies are needed of HPV infection in different populations.
The goal was to evaluate HPV prevalence and determinants in Concordia, Argentina.
A stratified random sample of 1786 households was obtained. Consenting women aged > or =15 years were interviewed and underwent examination, including colposcopy. Cells were collected for a Papanicolaou smear and HPV DNA testing with GP5+/6+ primer-mediated PCR-EIA.
PCR was performed on specimens from 987 women. Prevalence among women reporting no previous sexual activity was 3%, and among sexually active women it was 17.7%, peaking at <25 years of age and decreasing to a minimum at > or =65 years of age. However, low-risk types had similar prevalence (approximately 5%) in all age groups. HPV16 (4.0%), HPV35 (2.6%), and other high-risk types were the most common. Almost half of infections were multiple. Younger women initiated sexual activity earlier and had more partners. The main determinants of HPV detection were lifetime number of sex partners and vaginal discharge.
A clear pattern of decreasing prevalence of HPV with age was observed. This could be explained by development of immunity against specific types over time or related to a cohort effect associated with a recent spread of HPV in this population after recent changes in sexual behavior.
Infection with oncogenic human papillomavirus (HPV) types is a necessary cause of cervical cancer, the second most frequently occurring cancer in women worldwide. Rates of acquisition of HPV are high, particularly among sexually active young adults. Reported estimates of incident HPV infection among initially negative women have reached as high as 60% over a 5-year follow-up period. In this article, we review the epidemiology of HPV infection. In addition to estimates of disease frequency, we highlight risk factors for HPV infection, including the number of lifetime sex partners, which is the most salient risk factor. We discuss significant issues surrounding the natural history of HPV infection, including viral persistence versus clearance, immune response, development of lesions and development of cancer. Finally, we discuss strategies for preventing HPV infection.
The incidence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of highly active antiretroviral therapy (HAART). The prevalence of the putative anal cancer precursor, anal intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced. We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART.
A baseline point-prevalence analyses in a prospective cohort study of AIN was performed at a university-based research clinic. A total of 357 HIV-positive MSM with no history of anal cancer completed a questionnaire detailing behaviors and medical history, anal cytology and human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsy for detection of AIN.
Eighty-one percent of participants with available CD4+ cell counts at baseline had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95% confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were associated with AIN after adjustment for length of time participants were HIV-positive, CD4+ cell count and HIV viral load.
The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART. Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART.
HIV-positive men and women are at increased risk of anogenital and oral HPV infection. The risks for HPV-associated high-grade intra-epithelial neoplasia (IN) and cancer are also increased. The prevalence of oral, anal, and cervical HPV infection in HIV-positive individuals compared with HIV-negative individuals increases with progressively lower CD4+ levels, as does incident high-grade IN. In contrast to IN, development of cancer is not related to lower CD4+ level. With increasing grades of IN and cancer, the proportion of tissues with copy-number abnormalities (CNA) increases, with one of the most common genetic changes being amplification of chromosome 3q. The presence of CNA is associated with the integration of HPV DNA into the host genome, with loss of HPV E2 and/or E2 rearrangement. This suggests a link between CNA and increased HPV-induced chromosomal instability mediated through de-repressed E6 and E7 expression consequent to loss of functional E2 protein. In addition, epigenetic changes occur with increasing frequency in high-grade IN and cancer, such as hypermethylation leading to down-regulation of potential tumor suppressor genes. Analysis of these data together suggests that immune suppression plays a more prominent role in the earlier stages of HPV-associated disease, up to and including incident high-grade IN. Persistent high-grade IN and development of cancer may be more strongly related to the cumulative effect of HPV-associated genetic instability and the resulting host genetic changes. There are few data to suggest a direct role for HIV in the pathogenesis of HPV-associated neoplasia, but HIV-associated attenuation of HPV-specific immune responses may allow for persistence of high-grade IN and sufficient time for accumulation of genetic changes that are important in progression to cancer.
Rates of cervical and anal human papillomavirus (HPV) infection and abnormal cytology are high in HIV-infected women, as are rates of anal HPV infection and abnormal cytology in HIV-infected men who have sex with men (MSM). Available evidence indicates that the incidence of anal cancer in HIV-infected MSM has increased in association with prolonged life expectancy achieved with antiretroviral therapy. Routine screening for cervical neoplasia is recommended for HIV-infected women. Routine screening is not yet universally recommended for anal neoplasia, although it should be considered for at-risk patients, particularly given recent improvements in local treatments. A preventive vaccine against cervical HPV infection is approved for use in young women before onset of sexual activity and acquisition of HPV infection. Its potential benefit in preventing anal infection in women and men has yet to be determined, and its potential utility in those with HIV infection remains unknown. This article summarizes a presentation on HPV infection in HIV-infected patients made by Joel Palefsky, MD, at an International AIDS Society-USA Continuing Medical Education course in Chicago in May 2007. The original presentation is available as a Webcast at www.iasusa.org.
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