Anal Human Papillomavirus DNA Research Articles

Prevalence of Anal Human Papillomavirus Infection and Anal High-Grade Squamous Intraepithelial Lesions Among Men Who Have Sex With Men 50 Years and Older Living With or Without HIV.

Anal cancer is caused by human papillomavirus (HPV), particularly HPV-16, and is preceded by anal high-grade squamous intraepithelial lesions (HSILs). The incidence of anal cancer is highest among men who have sex with men (MSM) living with HIV (MSMLWH) and increases with age. However, most previous studies of anal HPV infection and anal HSIL were performed on men under 50 years old, and relatively little is known about HSIL among older MSMLWH or MSM not living with HIV (MSM-Not-LWH). We enrolled MSM who were aged 50+ during 2018-2022 in San Francisco, CA. One hundred twenty-nine MSMLWH and 109 MSM-not-LWH participated. All participants had anal HPV DNA testing (Atila Biosystems) and high-resolution anoscopy with a biopsy of visible lesions. Among MSMLWH, 47% had anal HSIL, 19% had HPV-16, and 51% had other oncogenic anal HPV types (excluding HPV-16). Among MSM-not-LWH, 37% had anal HSIL, 22% had HPV-16, and 34% had other oncogenic anal HPV types. Increasing age was not statistically associated with prevalent HSIL, HPV-16, or other oncogenic HPV infections in MSMLWH or MSM-not-LWH. HPV-16 (odds ratio: 45.1, 95% confidence interval: 15.8-129); other oncogenic HPV types (odds ratio: 5.95, 95% confidence interval: 2.74-12.9) were associated with increased odds of anal HSIL, adjusted for age, income, education, and HIV status. The prevalence of oncogenic anal HPV, anal HPV-16, and anal HSIL remains very high in older MSMLWH and MSM-not-LWH. With recent evidence showing that treating anal HSIL prevents anal cancer, MSM aged 50+ should be considered for anal cancer screening.

High Prevalence of Human Papillomavirus on Anal and Oral Samples from Men and Women with External Anogenital Warts: The HERCOLES Study.

Human papillomavirus (HPV) infection is highly prevalent in the sexually active population. This study estimates the prevalence of HPV DNA in anal and oral samples from a cohort of men and women with incident anogenital warts. Anal and/or oral samples from 541 patients with anogenital warts were tested for 35 HPV genotypes using a PCR assay. The overall prevalence of anal HPV and oral HPV DNA was 59.9% (n = 305/509; 95% confidence interval (CI) 55.6-64.1%) and 14.5% (n = 78/538; 95% CI 11.8-17.7%), respectively. Among patients with perianal warts, the anal HPV DNA prevalence was 92.3% (95% CI 87.0-95.5%). Anal HPV DNA prevalence in patients with genital warts but no perianal warts was 55.7% (95% CI 50.6-60.7%). Both anal and oral HPV infections were more common in men who have sex with men than in heterosexual men (90.4% versus 38.5% and 20.8% versus 11.8%, respectively). Anal high risk-HPV infection was more common in women (58.8%) and in men who have sex with men (67.7%). We found that anogenital warts represent a clinical marker for both anal and oral HPV infections, including anal high risk-HPV infections, particularly among women and men who have sex with men.

Incidence, Clearance, and Persistence of Anal Human Papillomavirus in Men Who Have Sex With Men Living With Human Immunodeficiency Virus: Implications for Human Papillomavirus Vaccination.

Men who have sex with men living with human immunodeficiency virus have a high risk of anal cancer. We estimate the likely benefit of human papillomavirus (HPV) vaccination among participants of the Anal Cancer Examination study. Anal swabs were collected for the detection and genotyping of anal HPV DNA by linear array (Roche Diagnostics) in this 2-year multicenter prospective cohort. We calculated the proportion of men, stratified by age, without detectable vaccine type-specific DNA. Overall, 255 men, with a median age of 50 years (interquartile range, 44-56 years) contributed 488.9 person-years of follow-up. After 2 years of follow-up, 149 (58%; 95% confidence interval [CI], 52-65) had at least 1 high-risk HPV (HRHPV), and 71 (28%, 95% CI, 22-34) had HPV types 16/18 detected. Assuming that DNA-negative men would receive vaccine protection, vaccination at baseline could potentially prevent HRHPV infection in 10.2% of men (95% CI, 6.8-14.6, 26 of 255) 2 years later from incident HRHPV covered by the bivalent and quadrivalent vaccine, and 29.4% of men (95% CI, 23.9-35.4, 75/255) from incident HRHPV covered by the nonavalent vaccine. Though there is high prevalence of anal HPV in men who have sex with men living with human immunodeficiency virus, there was also a high incidence of HRHPV vaccine types in the 2-year follow-up, indicating potential for prevention if these men were not previously infected with HPV vaccine types and were vaccinated at their baseline visit.

Anogenital human papillomavirus virus DNA and sustained response to the quadrivalent HPV vaccine in women living with HIV-1

ObjectivesPeople living with HIV have increased Human Papillomavirus (HPV) related lesions and malignancies. We describe HPV DNA recovered from the cervix and anal canal, explore the effect of vaccination on HPV detection, and examine the durability of vaccine titers in women living with HIV-1 who were vaccinated with the quadrivalent HPV vaccine. MethodsAIDS Clinical Trials Group A5240 was a prospective study of the quadrivalent HPV (qHPV) vaccine in 315 HIV-1 infected women in three CD4 strata (A: >350, B; 201–350, C: ≤200 cells/mm3). Vaccine was administered at entry, week 8 and week 24. Cervical and anal HPV DNA specimens were collected at baseline, weeks 28 and 52; serum for antibody testing was obtained at baseline, weeks 28 and 72. ResultsVaccine antibody titers decreased across all four HPV types at week 72 compared to week 28. Lower proportions of sustained seropositivity were observed in women with lower CD4 counts for all four vaccine types, with the lowest titers for HPV 18. Despite the decrease, the geometric mean titer levels were above the seroconversion cut-off levels for all types except HPV 18 in the lowest CD4 stratum. Of the 174 participants who had a negative baseline HPV 16 antibody and developed antibody response at week 28, 95%, 88%, and 86% retained seropositivity at week 72 in strata A, B, and C respectively. Lower antibody retention was observed in women with CD4 < 200 compared to CD4 > 350 (p = 0.016). Anal HPV detection was more prevalent compared to cervical detection at all visits. Among high risk types, type 52, 31, 16, 18 and 51 were the most common in the cervical compartment, while types 16, 35, 18, and 51 were the most prevalent in the anal canal at baseline (listed in the order of prevalence). Later detection of HPV not present at baseline was uncommon in either compartment. Serial recovery of HPV over time was more commonly observed in the anal canal. ConclusionThe qHPV vaccine elicits durable titer response above the seroconversion cut-off levels in HIV-infected women. However, the titer levels were substantially lower by Week 72, most noticeably in type 18. HPV DNA was detected more frequently in the anal canal. Detection of non-vaccine high risk HPV suggests a role for the nonavalent vaccine.

Human Papillomavirus Seroprevalence and Association with Anal HPV Infection and Squamous Intraepithelial Lesions in Australian Gay and Bisexual Men.

Background: Gay and bisexual men (GBM) are at disproportionately high risk of anal cancer. The precursor lesions, high-grade squamous intraepithelial lesions (HSIL), are very common and it is evident that not all HSIL progresses to cancer. The serologic response to anal human papillomavirus (HPV) in GBM has not been well characterized.Methods: The Study of the Prevention of Anal Cancer is an ongoing cohort study of GBM ages 35 years and older. At six visits over three years, anal samples are collected for cytology, HPV DNA testing, and histology. Baseline serum was tested for HPV L1, E6, and E7 antibodies for 10 HPV types. Seroprevalence and associated predictors were analyzed.Results: A total of 588 of 617 participants were included in this analysis. A total of 436 (74.2%) were seropositive for at least one of the 10 HPV types. Almost half had L1 antibodies to HPV6 (48.5%), over a third to HPV11 (36.4%) and HPV16 (34.5%). HIV-positive men were more likely to be HPV L1 seropositive. HSIL detection was highest among participants who were HPV serology and DNA positive. There was a borderline significant association between presence of HPV16 E6 antibodies and prevalent HSIL (OR = 2.97; 95% confidence interval, 0.92-9.60; P = 0.068).Conclusions: HPV L1 seropositivity was common in this cohort of older GBM. These results suggest that HPV L1 seropositivity, in conjunction with anal HPV DNA detection, predicts concurrent HSIL. The apparent association between HPV16 E6 antibodies and prevalent HSIL is a finding with potential clinical significance that needs further exploration.Impact: HPV seropositivity with concurrent DNA detection predicted anal HSIL detection. Cancer Epidemiol Biomarkers Prev; 27(7); 768-75. ©2018 AACR.

Anal Squamous Intraepithelial Lesions and HPV Among Young Black Men Who Have Sex with Men.

Limited data are available on anal squamous intraepithelial lesions (ASILs) and anal human papillomavirus (HPV) infection in young, Black populations. The purpose of this study was to examine the prevalence of and relationships between ASILs and high-risk HPV infection in a young (<30 years of age), predominantly Black, men who have sex with men (MSM) population. Results of anal cytology and HPV DNA were gathered for 83 individuals. Forty-two percent of individuals (35) had atypical squamous cells of undetermined significance and 33% (27) had low-grade squamous intraepithelial lesion by cytology. Only 9% tested positive for both high-risk HPV subtypes 16 and 18. Low rates of infection with both HPV types 16 and 18 may provide further evidence that we should continue to vaccinate young, Black MSM against HPV.

Incidence of and risk factors for type-specific anal human papillomavirus infection among HIV-positive MSM.

HIV-positive MSM are at increased risk of anal human papillomavirus (HPV) infection compared with men in the general population, and little is known about the natural history of anal HPV infection in this population. The objective of this study was to determine the incidence of and risk factors for anal type-specific HPV infection. Prospective cohort study. HIV-positive MSM were evaluated for anal HPV DNA, lifestyle factors, and sexual risk behaviors every 6 months for at least 2 years. The overall incidence rate of detectable type-specific anal HPV infection was 21.3 per 100 person-years [95% confidence interval (CI) 17.7-25.4] and was 13.3/100 person-years (10.5-16.6) for oncogenic HPV types. The most common incident infections were HPV 18 (3.7/100 person-years) and HPV 16 (3.5/100 person-years). An increased number of recent partners with whom the participant was the receptive partner [odds ratio (OR) 2.9 (1.6-5.1) 8+ partners vs. 0-1], an increased number of new partners in which the participant was the receptive partner [OR 1.03 (1.01-1.1) per partner], an increased number of new oral-anal contact partners in which the participant was the receptive partner [OR 1.1 (1.03-1.1) per partner], and the frequency of receptive anal intercourse [OR 1.1 (1.03-1.1) per act] all significantly increased the odds of incident HPV infection (P ≤ 0.05). HIV-positive MSM have a high incidence of oncogenic anal HPV infection. Recent receptive anal sexual behaviors, including receptive anal intercourse and receptive oral-anal contact, are the most important risk factors for incident anal HPV infection.

Coexisting anal human papilloma virus infection in heterosexual women with cervical HPV infection

To evaluate the prevalence of coexisting anal human papillomavirus (HPV) infection and concordance of HPV types in women with cervical HPV infection and to investigate the possible predictors for anal HPV infection. Study group was composed of women referred with documented cervical HPV infection. All patients had undergone anal HPV DNA testing. One hundred and six patients presenting with cervical HPV infection were eligible for the study. Overall, 24 and 20 distinct HPV genotypes were detected from cervical and anal specimens, respectively. We observed a considerably high prevalence (51.9%) of coexisting anal HPV infection in our study group. A majority of the women who were found to have anal HPV infection were infected with oncogenic or probable oncogenic types (64.6%). There were 20.0 and 58.3% rate of total and partial concordance between the two sites, respectively. We found that no demographic parameter but history of anal intercourse was related with the risk of anal HPV infection. Women with cervical HPV infection have a considerable risk for coexisting anal HPV infection. Concordance of HPV types infecting the cervix and anal canal is relatively high. There is no strong predictor for anal HPV infection in this population.

Lack of regression of anal squamous intraepithelial lesions despite immune restoration under cART

A high prevalence of anal squamous intraepithelial lesions (ASIL) and human papillomavirus (HPV) infections were observed in HIV-infected men who have sex with men (MSM) in the precART (combined antiretroviral therapy) era. The impact of cART on the natural history of HPV infection and ASIL is poorly documented. Ninety-four HIV-infected MSM naive of cART were enrolled in a longitudinal study before starting cART. Patients were evaluated for anal cytology, histology and anal HPV DNA at baseline, month 12 and month 24 of cART. HPV DNA genotyping was performed by Linear Array assay. Anal cytologic samples were processed by the Thin Prep method. Analyses included 76 patients with at least two visits with available cytology. The median age was 39.4 years. The median (interquartile range) CD4 cell count was 301 cells/μl (242-339) at baseline and 545 cells/μl at month 24, when 93% of patients had plasma HIV-RNA 50 copies/ml or less. An abnormal result was observed in 45 of 76 patients at baseline (59%) with prevalent low-grade squamous intraepithelial lesion (LSIL) in 27 patients (36%) and high-grade squamous intraepithelial lesion (HSIL) in seven patients (9%) and in 36 of 69 patients assessed at month 24 (52%) with LSIL in 23 patients (33%) and HSIL in six patients (9%). At month 24, regression of the severity of lesions was observed in 44% of patients, whereas a lesion occurred in 37% of patients. Our results show a high prevalence and incidence of ASIL in HIV-infected MSM despite immune restoration under cART. These data emphasize that HIV-positive MSM although receiving effective cART remain at high risk of anal squamous intra-epithelial lesions.

Anal human papillomavirus DNA in women at a colposcopy clinic

To describe the type-specific prevalence of anal and cervical human papillomavirus (HPV) infections and the cytology in HIV-negative women without a history of cervical cancer, attending a colposcopy clinic. To examine if an HPV positive anal smear is related to anal pathology and consequently indicative for further examinations (high resolution anoscopy, anal biopsy). From 149 consecutive women an anal swab and a cervical swab were taken, using the Cervex-Brush. The presence of 18 different HPV genotypes was determined using TaqMan-based real-time quantitative PCR targeting type-specific sequences of viral genes. From the fluid containing the cellular material, a liquid-based cytology sample was prepared of both collections with the robotic BD PrepStain Slide Processor. All slides were pre-screened by BD FocalPoint system and categorized from quintiles 1 to 5 and afterwards screened using targeted microscopic interpretation of selected suspicious fields using FocalPoint guided screening review stations. The 2001 Bethesda System Terminology was used for the anal slides. Ninety-six anal samples and all 149 cervical samples were adequate. Overall presence of HPV in the anus was 56.3% and in the cervix 53.7%. Overall, cytological abnormalities were found in 10.8% of anal smears and in 32.8% of cervical smears. HPV genotypes were identified in 47 samples on both sites: partial or complete concordance was found in 85.1%. HPV types 6, 16 and 18 were found in 27.9% and in 26.6% of the anal and cervical samples, respectively. The top three HPV types in the anus were 16, 51 and 39; in the cervix 16, 39, 51 and 56 (a shared 3(rd) place). HPV type 11 was not found. The presence of HPV genotypes is clearly multifocal in this study population of women attending a colposcopy clinic, with high concordance of genotypes. The number of anal HPV infections is high. Although cytological abnormalities are rare, the presence of HPV may lead to anal lesions later in life. From this perspective, complementary medical history and clinical examination of the anal region are advised.

Management of Anal Squamous Intraepithelial Lesions

Anal squamous intraepithelial lesions include both low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and are caused by chronic infection with the human papillomavirus (HPV). The disease is increasing in both incidence and prevalence, especially among patients with the following risk factors: homosexual men, acquired or iatrogenic immunosuppression, and presence of other HPV-related diseases. Although the natural history of the disease is unknown, there is significant evidence that untreated HSIL progresses to squamous cell carcinoma in 11% of patients and in up to 50% of patients with extensive disease and immunosuppression. Anal cytology and reflex HPV DNA testing are used to screen for disease, particularly among patients with the aforementioned risk factors. Evaluation of the patient should include physical examination and high-resolution anoscopy (HRA) to evaluate for disease above and below the dentate line. Intervention is warranted and this can be achieved in many ways. The treatment option associated with the best outcomes is ablation directed with HRA, which can be performed in the office or in the operating room with minimal morbidity. This strategy is effective in patients with both low-volume and high-volume disease and is associated with a malignant progression rate of 0.4% in patients with treated HSIL.

A trial of SGN-00101 (HspE7) to treat high-grade anal intraepithelial neoplasia in HIV-positive individuals

To test a therapeutic vaccine consisting of a fusion of the human papillomavirus (HPV) 16 E7 protein and the Mycobacterium bovis heat shock protein 65 (SGN-00101) to treat high-grade anal intraepithelial neoplasia (HG-AIN) in HIV-positive individuals. A phase I/II trial with three cohorts of five participants each, sequentially assigned to receive 100, 500 or 1000 microg SGN-00101, injected three times subcutaneously in alternating thighs at 4-week intervals. Anal disease was assessed at baseline, 8, 12, 24 and 48 weeks and was classified as the more severe of anal cytology and anal biopsy. Anal HPV DNA was detected using L1 consensus primer-based PCR followed by type-specific probing and dot-blot hybridization (DBH). HPV16, 18 and 31 DNA copy numbers were measured using quantitative real-time PCR. University-based research clinic. Thirteen HIV-positive men and two HIV-positive women with HG-AIN. There were no drug-related serious adverse events or significant changes in HIV viral load and CD4/CD8 ratio. At 48 weeks, two of five participants in both the 100 and 500 microg cohorts regressed to AIN 1 and one of five participants in the 1000 microg cohort regressed to atypical squamous cells of undetermined significance (ASC-US). All participants had at least one oncogenic HPV type at baseline. Three of five (60%) participants who regressed to AIN 1 or ASC-US became HPV-negative using DBH and real-time PCR, compared with none of 10 participants with no clinical response (P = 0.02). SGN-00101 was well tolerated in HIV-positive individuals, with preliminary evidence for clinical activity.

Effect of Highly Active Antiretroviral Therapy on the Natural History of Anal Squamous Intraepithelial Lesions and Anal Human Papillomavirus Infection

The effect of highly active antiretroviral therapy (HAART) on the natural history of anal squamous intraepithelial lesions (ASIL)-the likely anal cancer precursor-and anal human papillomavirus (HPV) infection is unknown. ASIL severity and level of anal HPV DNA were evaluated among HIV-positive men who have sex with men (MSM) for at least 6 months before initiation of HAART. The results were compared with those from a 6-month period after initiation of HAART. Anal swabs for cytology and HPV studies were obtained, followed by high-resolution anoscopy and biopsy. Among men whose most severe pre-HAART diagnosis was atypical squamous cells of undetermined significance or low-grade ASIL, 18% (confidence interval [CI], 6-31%, 7 of 38) progressed and 21% (CI, 8-34%, 8 of 38) regressed 6 months after starting HAART. Seventeen percent (CI, 0-38%, 2 of 12) of study subjects who began with a normal diagnosis developed ASIL. Only 4% (CI, 0-10%, 1 of 28) of study subjects with high-grade ASIL regressed to normal. There was no reduction in the proportion of study subjects who tested positive for HPV DNA or HPV DNA levels after HAART initiation. The ASIL and HPV data were similar to those of the pre-HAART comparison period. These results indicate that HAART has little effect on either ASIL or HPV in the first 6 months after HAART initiation.

Prevalence and risk factors for anal human papillomavirus infection in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women.

Little is known about the epidemiology of anal human papillomavirus (HPV) infection in women. We studied 251 human immunodeficiency virus (HIV)-positive and 68 HIV-negative women for the presence of anal HPV by use of polymerase chain reaction (PCR) and hybrid capture. Medical and behavioral risk factors were evaluated; 76% of HIV-positive and 42% of HIV-negative women were found to have anal HPV DNA via analysis by PCR (relative risk [RR], 1.8; 95% confidence interval [CI], 1.3-2.5). Among 200 women for whom there were concurrent anal and cervical HPV data, anal HPV was more common than cervical HPV in both HIV-positive (79% vs. 53%) and HIV-negative women (43% vs. 24%). By multivariate analysis of HIV-positive women, CD4(+) cell counts </=200 cells/mm(3), compared with counts >500 cells/mm(3) (RR, 1.4; 95% CI, 1.1-1.5), and cervical HPV infection (RR, 1.3; 95% CI, 1.1-1.4) were associated with anal HPV infection. Women >45 years old had reduced risk, compared with women <36 years old (RR, 0.80; 95% CI, 0.50-0.99), as did African American women (RR, 0.86; 95% CI, 0.72-1.0), compared with white women. Anal HPV infection is underrecognized in HIV-positive and high-risk HIV-negative women.

Determinants of human immunodeficiency virus DNA and RNA shedding in the anal-rectal canal of homosexual men.

To define the determinants of anal-rectal shedding of human immunodeficiency virus (HIV) DNA and RNA, 374 HIV-seropositive homosexual men were tested. Factors independently associated with detection of anal-rectal HIV DNA included anal-rectal inflammation and detection of anal human papillomavirus DNA; predictors of HIV RNA included detection of anal-rectal HIV DNA, anal-rectal inflammation, and high plasma HIV RNA levels. The latter (>10,000 copies/mL) was the main determinant of anal-rectal HIV RNA shedding when HIV DNA (e.g., HIV-infected cells) was not detected in the anal-rectal sample. The local presence of HIV-infected cells and local inflammation were the principal determinants of HIV RNA among those with low (<10,000 copies/mL) plasma HIV RNA load. Among those with anal-rectal HIV DNA present, increased HIV RNA plasma load did not increase the risk of shedding of HIV RNA into the anal-rectal canal.

Prevalence and risk factors for human papillomavirus infection of the anal canal in human immunodeficiency virus (HIV)-positive and HIV-negative homosexual men.

One of the groups at highest risk of anal cancer is homosexual and bisexual men. Like cervical cancer, anal cancer is associated with human papillomavirus (HPV) infection. Anal HPV infection was characterized in a study of 346 human immunodeficiency virus (HIV)-positive and 262 HIV-negative homosexual and bisexual men. Anal HPV DNA was detected in 93% of HIV-positive and 61% of HIV-negative men by polymerase chain reaction. The spectrum of HPV types was similar in HIV-positive and HIV-negative men, with HPV-16 the most common type. Infection with multiple HPV types was found in 73% of HIV-positive and 23% of HIV-negative men. Among HIV-positive men who were positive by hybrid capture for group B HPV types (16/18/31/33/35/39/45/51/52/56/58) or group A types (6/11/42/43/44), lower CD4 cell levels were associated with higher levels of group B DNA (P = .004) but not group A DNA. These data suggest increased replication of the more oncogenic HPV types with more advanced immunosuppression.

Prevalence of anal human papillomavirus infection and anal cytologic abnormalities in HIV-seropositive women.

To determine the prevalence of anal human papillomavirus (HPV) infections and anal cytologic abnormalities in HIV-seropositive and HIV-seronegative women. This cross-sectional study of a cohort of women with known HIV serostatus involved a standardized interview and a gynecologic examination, including a cytologic evaluation of the cervix and anus. Anal swabs were tested for HPV DNA using the Hybrid Capture assay. Two HIV/AIDS clinics, a sexually transmitted disease clinic, a methadone clinic and women enrolled in a study of HIV heterosexual transmission in the greater New York City metropolitan area. One hundred and two HIV-seropositive and 96 HIV-seronegative women were selected from an ongoing study of the gynecologic manifestations of HIV infection. Detection of anal HPV DNA and anal cytologic abnormalities. Anal cytologic abnormalities were detected in 27 (26%) of the 102 HIV-seropositive women and in six (7%) of 96 HIV-seronegative women. Five (5%) of the anal smears from the HIV-seropositive women and one (1%) from the HIV-seronegative women had low-grade anal intra-epithelial neoplasia. The remainder of the anal cytologic abnormalities were classified as mild squamous cytologic atypia. HPV DNA was detected in 30 (29%) of 102 HIV-seropositive and two (2%) of 96 HIV-seronegative women. Of the 33 patients with anal cytologic abnormalities, 19 (58%) had anal HPV DNA detected as compared to 13 (8%) of 160 women without cytologic abnormalities (P < 0.001). In a multivariate logistic regression analysis, HIV-seropositivity was found to be an independent risk factor for both anal HPV infection and anal cytologic abnormalities and the strength of the association was greater in women with lower CD4+ T-lymphocyte counts. The prevalence of both anal cytologic abnormalities and anal HPV infection are significantly increased in HIV-seropositive women.

Association of anal dysplasia and human papillomavirus with immunosuppression and HIV infection among homosexual men.

To examine and quantify the association between anal squamous intraepithelial lesions (ASIL), anal human papillomavirus (HPV) infection and immunosuppression among HIV-seropositive and HIV-seronegative homosexual men. Cross-sectional study among homosexual men presenting at a community-based clinic for HIV serologic screening. Anal HPV DNA was detected in 55 and 23% of 285 HIV-seropositive and 204 HIV-seronegative men, respectively, by Southern transfer hybridization (STH) [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.7-6.2], and in 92 and 78% by polymerase chain reaction (PCR) (OR, 3.1; 95% CI, 1.6-5.8). ASIL was noted in 26% of HIV-seropositive men and in 8% of HIV-seronegative men (compared with men with negative cytologic findings: OR, 5.6; 95% CI, 3.0-10.5), with high-grade lesions noted in 4% of HIV-seropositive and in 0.5% of HIV-seronegative men. Among HIV-infected men, ASIL, detection of specific anal HPV types, and detection of high levels of anal HPV DNA (i.e., levels of HPV DNA detectable by both STH and PCR) were all associated with immunosuppression. Nevertheless, HIV-seropositive men with CD4 counts > 500 x 10(6)/l had a higher prevalence of both anal HPV and ASIL than men without HIV infection. Overall, detection of HPV at high levels was associated with ASIL. However, after adjustment for level of detectable HPV DNA, the risk of ASIL among HIV-seropositive men with CD4 counts < 500 x 10(6)/l was increased 2.9-fold (95% CI, 1.4-6.2) over that of HIV-seropositive men with CD4 counts > 500 x 10(6)/l. Given the high rates of ASIL in HIV-seronegative and both immunosuppressed and non-immunosuppressed HIV-seropositive homosexual men, natural history studies are now needed to assist in the development of strategies for the detection and management of such lesions. The increased prevalence of ASIL seen among immunosuppressed HIV-seropositive men may be the result of both a non-specific increase in productive HPV infection and HIV-induced immune alterations of HIV-related neoplasia.

NATURAL HISTORY OF ANAL CYTOLOGIC ABNORMALITIES AND PAPILLOMAVIRUS INFECTION AMONG HOMOSEXUAL MEN WITH GROUP IV HIV DISEASE

Previous studies have demonstrated a high prevalence of anal cytologic abnormalities as well as anal human papillomavirus (HPV) infection among homosexual men with group IV HIV disease. However, the natural history of these changes in this population has not yet been studied. To this end, 37 homosexual men with group IV HIV disease attending an outpatient HIV clinic were followed at approximately 9-month intervals for an average of 17 months, using anal cytology, anoscopy, anal biopsy, and anal HPV DNA hybridization. During the study, the proportion of the 37 subjects with anal cytologic abnormalities increased from 27 to 65%. The proportion of subjects with any grade of anal intraepithelial neoplasia rose from 8 to 32%, with high-grade anal intraepithelial neoplasia increasing from 0 to 16%. The proportion of subjects with anal HPV infection increased from 60 to 89%, and infection with multiple HPV types was noted in at least 48%. We conclude that a large proportion of homosexual men with group IV HIV disease develop anal cytologic abnormalities, including anal intraepithelial neoplasia, over a short period of time. Together with a rapidly increasing incidence of anal cancer among single, never-married men in the San Francisco Bay area, these results suggest that these men may be at significant risk of development of anal cancer.

Association of Human Immunodeficiency Virus and Anal Human Papillomavirus Infection Among Homosexual Men

A previous study of men with proctitis, proctocolitis, or enteritis showed an association of anal human papillomavirus (HPV) infection with human immunodeficiency virus (HIV) infection. Because anorectal abnormalities may confound an observed association between anal HPV DNA and HIV seropositivity, the present study was undertaken among consecutive homosexual men seeking HIV serologic testing who were unselected for anorectal symptoms. Consecutive homosexual men underwent a standardized interview, physical examination, and collection of specimens for HIV serologic testing and detection of anal HPV DNA. Anal HPV DNA was detected in eight (31%) of 26 HIV-seropositive men and in 10 (8%) of 119 HIV-seronegative men (odds ratio, 5.8; 95% confidence interval, 1.1 to 30.1, adjusted for history of sexually transmitted disease, current anorectal symptoms, and age). When men with anorectal symptoms were excluded from the analysis, anal HPV DNA was detected in 27% of seropositive men compared with 8% of seronegative men (odds ratio, 4.4; 95% confidence interval, 1.4 to 13.4). There was no difference between HIV-seropositive and HIV-seronegative men with respect to distribution of type of HPV DNA. Men with group II or III and group IV HIV disease were 4.1 and 10.9 times, respectively, more likely than HIV-seronegative men to have anal HPV DNA detected. Because HIV-seropositive men appear to be at increased risk for the detection of anal HPV DNA, the natural course of anal HPV infection should be compared among HIV-seropositive and HIV-seronegative homosexual men.