Search

Summary Background The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16–26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. Methods The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16–23 years) or men who have sex with men (MSM; aged 16–26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov , NCT00090285 . Findings Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1–11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0–6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0–8·7) versus 137·3 (83·9–212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0–7·7) versus 140·4 (89·0–210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5–114·4) versus 906·2 (553·5–1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6–212·3] vs 0 cases per 10 000 person-years [0·0–13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0–215·7] vs 0 cases per 10 000 person-years [0·0–10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9–1289·1] vs 101·3 cases per 10 000 person-years [32·9–236·3]). No vaccine-related serious adverse events were reported. Interpretation The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. Funding Merck Sharp & Dohme.

Background In men, the incidence of human papillomavirus (HPV)–related cancer is rising, but data regarding male HPV infection and seroprevalence are available from only a few countries. Methods This analysis of a global HPV vaccine trial evaluated baseline data from 1399 human immunodeficiency virus–negative heterosexual men (HM) and men who have sex with men (MSM). Key objectives included assessment of HPV prevalence and risk factors for seropositivity to 9-valent HPV (9vHPV) vaccine types (6, 11, 16, 18, 31, 33, 45, 52, and 58), and concordance between seropositivity and prevalent HPV type. Results Overall, 455 of 3463 HM (13.1%) and 228 of 602 MSM (37.9%) were HPV DNA positive for any 9vHPV vaccine type at baseline. Infection prevalence and seroprevalence (≥1 9vHPV vaccine type) were 13.2% and 8.1%, respectively, among 333 HM from Europe, and 37.9% and 29.9%, respectively, among 335 MSM from Europe or North America. Among men with baseline infection, MSM had higher seroprevalence for concordant HPV types (39.5% vs 10.8% in HM). The seropositivity risk (irrespective of baseline infection status) was higher among MSM versus HM (age-adjusted odds ratio, 3.0 [95% confidence interval, 2.4–6.4]). Among MSM, statistically significant seropositivity risk factors included younger age at sexual debut, higher number of receptive anal sex partners, and less frequent condom use. No factors assessed were associated with seropositivity in HM. Conclusions Higher proportions of MSM than HM were HPV DNA positive and seropositive, and concordance between HPV DNA positivity and seropositivity, a potential marker of true infection versus carriage, was higher in MSM. Most MSM and HM were seronegative for all 9vHPV vaccine types, suggesting the potential benefit of catch-up vaccination after sexual debut. Clinical Trials Registration. NCT00090285.

Background The progression rate and predictors of anal dysplastic lesions to squamous cell carcinoma of the anus remain unclear. Characterizing these parameters may help refine anal cancer screening guidelines. Objective This study aimed to determine the rate of progression of high-grade anal dysplasia to invasive carcinoma in HIV-infected persons. Design Using the Surveillance, Epidemiology, and End Results database linked to Medicare claims from 2000 to 2011, we identified HIV-infected subjects with incident anal intraepithelial neoplasia III. To estimate the rate of progression of anal intraepithelial neoplasia III to invasive cancer, we calculated the cumulative incidence of anal cancer in this cohort. We then fitted Poisson models to evaluate the potential risk factors for incident anal cancer. Settings This is a population-based study. Patients Included were 592 HIV-infected subjects with incident anal intraepithelial neoplasia III. Main outcome measures The primary outcome measured was incident squamous cell carcinoma of the anus. Results Study subjects were largely male (95%) with a median age of 45.7 years. Within the median follow-up period of 69 months, 33 subjects progressed to anal cancer. The incidence of anal cancer was 1.2% (95% CI, 0.7%-2.5%) and 5.7% (95% CI, 4.0%-8.1%) at 1 and 5 years, following a diagnosis of anal intraepithelial neoplasia III. Risk of progression did not differ by anal intraepithelial neoplasia III treatment status. On unadjusted analysis, black race (p = 0.02) and a history of anogenital condylomata (p = 0.03) were associated with an increased risk of anal cancer incidence, whereas prior anal cytology screening was associated with a decreased risk (p = 0.04). Limitations The identification of some incident cancer episodes used surrogate measures. Conclusions In our population-based cohort of HIV-infected subjects with long-term follow-up, the risk of progression from anal intraepithelial neoplasia III to anal squamous cell carcinoma was higher than reported in other studies and was not associated with the receipt of anal intraepithelial neoplasia III treatment. See Video Abstract at http://links.lww.com/DCR/A933.

[Background] Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality., [Methods] We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models., [Findings] The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15–18 years and 28·8% (141 of 490) among those age 23–24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25–34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend, [Interpretation] High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+., International Agency for Research on Cancer.

Background Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)–related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. Methods Two hundred and sixty MSMLWH aged 18–26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. Results Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type–associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18–associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. Conclusions 18–26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type–associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination., A high proportion of 18-26 year-old men-who-have-sex-with-men-living-with-HIV screened for a quadrivalent HPV (qHPV) vaccine trial had anal low-grade/high-grade squamous intraepithelial lesions (LSIL/HSIL). Vaccinees naive to qHPV types were protected against incident qHPV type-associated-LSIL/HSIL. Vaccination before sexual initiation is critically important.

BACKGROUND HIV-positive individuals have high incidence of anal high-grade squamous intraepithelial lesions (HSIL) at the squamocolumnar junction (SCJ), which can progress to cancer. Focal radiofrequency ablation (RFA) treats HSIL, but metachronous recurrence remains high and may be improved with circumferential treatment. SETTING The study was performed at a single center. METHODS This was a prospective trial of circumferential anal RFA using Barrx 60 RFA focal catheters in participants with ≥1 anal SCJ HSIL. The entire SCJ was ablated by RFA. Adverse events (AEs), symptoms, including pain, and quality of life were assessed. High-resolution anoscopy assessed recurrences at 3, 6, 9, and 12 months. Lesion site biopsies occurred at month 12. Recurrences were retreated with focal RFA. RESULTS Ten male participants (9 HIV+), with a median 2 HSILs (range 2-8) each, enrolled. Median T-cell count and viral load were 730 cells/mcL and 38 copies/mL. Median duration of RFA treatment was 6.5 (5-13) minutes. Lesion persistence occurred in 4 participants (3 at 3 months, 1 at 6 months). Recurrence at a new site occurred in 1 participant at 3 months. No lesion persisted after retreatment. All participants were HSIL free and completely healed by 12 months. Two device-related mild AEs occurred in 1 participant each (thrombosed external hemorrhoid and soft anal scar; both resolved). No serious AEs occurred. CONCLUSION Circumferential anal SCJ RFA produced total HSIL eradication with no more than 2 treatments. Circumferential RFA seems to be well tolerated with minimal pain and no serious AEs in HIV+ participants. CLINICALTRIALS.GOV:: NCT02189161.

Importance Outcomes of treating high-grade squamous intraepithelial lesions (HSIL), a precursor to anal cancer, remain uncertain. Emerging evidence shows that post HSIL treatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves the effectiveness of treatment. However, no recommendations exist regarding the use of qHPV vaccine as an adjuvant form of therapy. Our objective was to determine whether post-treatment adjuvant vaccination should be adopted in HIV-infected MSM (individuals at highest risk for anal cancer) on the basis of cost-effectiveness determined using existing evidence or whether future research is needed. Methods We developed a Markov (state-transition) cohort model to assess the cost-effectiveness of post-treatment adjuvant HPV vaccination of 27 years or older HIV-infected MSM. We first estimated cost-effectiveness and then performed value-of-information (VOI) analysis to determine whether future research is required by estimating the expected value of perfect information (EVPI). We also estimated expected value of partial perfect information (EVPPI) to determine what new evidences should have highest priority. Results With the incremental cost-effectiveness ratio (ICER) of $71,937/QALY, “treatment plus vaccination” was the most cost-effective HSIL management strategy using the willingness-to-pay threshold of 100,000/QALY. We found that population-level EVPI for conducting future clinical research evaluating HSIL management approaches was US$12 million (range $6–$20 million). The EVPPI associated with adjuvant qHPV vaccination efficacy estimated in terms of hazards of decreasing HSIL recurrence was $0 implying that additional data from a future study evaluating efficacy of adjuvant qHPV vaccination will not change our policy conclusion that “treatment plus vaccination” was cost-effective. Both the ICER and EVPI were sensitive to HSIL treatment compliance. Conclusion Post-treatment adjuvant qHPV vaccination in HIV-infected MSM aged 27 or above is likely to be cost-effective. Use of adjuvant qHPV vaccination could be considered as a potential strategy to reduce rising anal cancer burden among these high-risk individuals.

Author(s): Stier, Elizabeth A; Lensing, Shelly Y; Darragh, Teresa M; Deshmukh, Ashish A; Einstein, Mark H; Palefsky, Joel M; Jay, Naomi; Berry-Lawhorn, J Michael; Wilkin, Timothy; Wiley, Dorothy J; Barroso, Luis F; Cranston, Ross D; Levine, Rebecca; Guiot, Humberto M; French, Audrey L; Citron, Deborah; Rezaei, M Katayoon; Goldstone, Stephen E; Chiao, Elizabeth | Abstract: BackgroundWomen living with human immunodeficiency virus (WLHIV) have disproportionately high rates of squamous cell carcinoma of the anus compared with the general population of women. Anal high-grade squamous intraepithelial lesions (HSILs) precede anal cancer, and accurate studies of HSIL prevalence among WLHIV in the United States are lacking.MethodsThe AIDS Malignancy Consortium 084 study was a multicenter national trial to evaluate the prevalence of and risk factors for anal HSIL in a US cohort. Eligible participants were WLHIV aged ≥18 years with no history of anal HSIL. Study participants had an examination including collection of cervical/vaginal and anal specimens, followed by high-resolution anoscopy with biopsy.ResultsWe enrolled 256 women with evaluable anal pathology. The mean age was 49.4 years, 64% women were non-Hispanic black, 67% were former or current smokers, and 56% reported ever having anal sex with a man. The median CD4 T-cell count was 664 cells/μL. The prevalence of anal histologic HSIL (hHSIL) was 27% (95% confidence interval [CI], 22%-33%). There was a strong concordance (240/254) between local and consensus pathologists for hHSIL vs less than hHSIL (κ = 0.86 [95% CI, .79-.93]). Current CD4 count of ≤200 cells/μL was the strongest predictor of consensus anal hHSIL diagnosis (adjusted odds ratio [aOR], 10.34 [95% CI, 3.47-30.87]). History of anoreceptive intercourse was also associated with hHSIL (aOR, 2.44 [95% CI, 1.22-4.76]).ConclusionsThe prevalence of anal hHSIL in WLHIV in the United States was 27% in this study where all participants received high-resolution anoscopy and biopsy.

We examined the prevalence of infection with human papillomavirus (HPV) and HIV in a cohort of young gay, bisexual, and other men who have sex with men [sexual minority men (SMM)]. HPV vaccination uptake was assessed; HIV antibody testing was performed and genetic testing for oral and anal HPV infection was undertaken. We examined both HPV vaccination and infection in relation to key demographic and structural variables. Participants (n = 486) were on average 23 years old; 70% identified as a member of a racial/ethnic minority group, and 7% identified as transgender females. Only 18.1% of the participants indicated having received the full dosage of HPV vaccination and 45.1% were unvaccinated. Slightly over half the participants (58.6%) were infected with HPV, with 58.1% testing positive for anal infection and 8.8% for oral infection. HIV seropositivity was associated with infection to oral HPV [adjusted odds ratio (AOR) = 4.03] and vaccine-preventable HPV, whereas both neighborhood-level poverty (AOR = 1.68) and HIV infection (AOR = 31.13) were associated with anal infection to HPV (AOR = 1.68). Prevalence of HPV infection is high among unvaccinated young SMM, despite the availability and eligibility for vaccination. HPV infection adds further health burden to these populations and is particularly concerning for those who are HIV positive as HIV infection increases the risk of developing HPV-related cancers. These findings underscore a missed prevention opportunity for an at-risk and underserved population and suggest the need for active strategies to increase HPV vaccination uptake in young SMM before the onset of sexual behavior.

Anal canal high-grade squamous intraepithelial lesion (HSIL) is the precursor to anal cancer. Immunocompromised patients are at increased risk and disease is usually within 3 cm from the anal verge. High-resolution anoscopy (HRA) with an 8-cm anoscope is used to identify and guide cautery treatment of HSIL. We report three patients with a long-term history of ulcerative colitis (UC) treated with systemic immunomodulators who developed proximally located rectal HSIL. Two patients were HIV-negative women, 63 and 48 years old, and the third was a 51-year-old HIV-positive man with underlying UC for 10, 16, and 3 years, respectively. They each presented with a HPV-positive HSIL visibly extending above the limits of the anoscope used for HRA. None developed cancer. All had episodes of active UC. It is unclear what causative role systemic immunomodulators play in predisposing UC patients to proximal HSIL. HSIL probably developed on a tongue of HPV-infected squamous epithelium growing proximally over the inflamed rectum. Islands developed when areas of squamous epithelium degenerated, creating skip areas. This study highlights the potential for HSIL to extend into the rectum either as a contiguous patch or isolated islands and the need for heightened surveillance in patients with extensive anal canal HSIL treated with immunodulator therapy. HSIL identified at the limit of the anoscope should be investigated further with colonoscopy, and argon plasma coagulation (APC) ablation can serve as an effective treatment option. Patients are at risk for stricture, but it is unclear what role the UC or the ablation played in stricture formation.

PurposeRadiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia, but its efficacy in treating anal canal high-grade squamous intraepithelial lesions (HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy of applying hemi-circumferential RFA to anal canal HSIL.MethodsTwenty-one HIV-negative participants with HSIL occupying ≤half the anal canal circumference were treated with hemi-circumferential anal canal RFA. Participants were assessed every 3months for 12months with high-resolution anoscopy; recurrence in the treatment zone was re-treated with focal RFA.ResultsTwenty-one participants with a mean of 1.7 lesions (range 1-4) enrolled and completed the trial. Six (29%) participants had recurrent HSIL within the treated hemi-circumference within 1year. Four participants (19%) had persistence of an index lesion at 3months. One (2.9%) index HSIL persisted again at 12months. No participants had more than two RFA treatments. KM curve-predicted HSIL-free survival within the treatment zone at 1year was 76% (95% CI 52-89%). Comparing the first 7 and last 14 participants, the predicted 1-year HSIL-free survivals are 43% (95% CI 10-73%) and 93% (95% CI 59-99%), respectively (p=0.008), suggesting a learning curve with the treating physician. Multivariable analysis showed decreased recurrence in the last 14 participants (HR 0.02; 95% CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95% CI 1.01-2.01). No participants had device or procedure-related serious adverse events, anal stricture, or heavy bleeding.ConclusionsHemi-circumferential RFA yielded a high rate of anal HSIL eradication in HIV-negative patients at 1year with minimal adverse events. Lesion persistence was probably related to incomplete initial ablation.

BACKGROUND More than 90% of anal cancers are caused by human papillomavirus, and human papillomavirus strains 16 and 18 are the most oncogenic. Anal high-grade squamous intraepithelial lesions are cancer precursors. Treating these high-grade intraepithelial lesions likely reduces the risk of cancer, but cytology is an imperfect screening test. OBJECTIVE The purpose of this study was to determine whether human papillomavirus 16 and/or 18 testing better predicts the presence of high-grade squamous intraepithelial lesions. DESIGN In this retrospective study, 894 consecutive patients underwent anal dysplasia screening with digital anorectal examination, anal cytology, high-risk human papillomavirus testing, and high-resolution anoscopy with biopsy. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of each test and for a novel screening protocol. The absolute and relative risk of high-grade squamous intraepithelial lesions for all of the cytology/human papillomavirus combinations were also calculated. SETTINGS The study was conducted at a single practice specializing in anal dysplasia. PATIENTS Ninety-two percent of participants were men who have sex with men. Forty-four percent were HIV-positive individuals who were well controlled on antiretroviral therapy. The median age was 50 years. MAIN OUTCOME MEASURES The presence of high-grade squamous intraepithelial lesions as a function of human papillomavirus and the cytology results were measured. RESULTS High-risk human papillomavirus testing alone demonstrated better sensitivity (96% vs 89%; p = 0.03) and negative predictive value (99% vs 96%; p = 0.008) over cytology. Human papillomavirus 16/18 testing increased specificity (48% to 71%; p < 0.0001) and positive predictive value (24% to 37%; p = 0.003) over testing for all of the high-risk strains. For each cytology category, high-grade squamous intraepithelial lesions were more prevalent when human papillomavirus 16/18 was detected. Benign cytology with 16/18 had a 31-fold increased risk of high-grade squamous intraepithelial lesions. LIMITATIONS This study was conducted in a single private practice specializing in anal dysplasia screening with a mostly male population, and results might not be generalizable. CONCLUSIONS Testing of high-risk human papillomavirus strains 16/18 improves specificity and positive predictive value over cytology for anal dysplasia screening. Patients testing positive for strains 16/18 are at a high risk for high-grade squamous intraepithelial lesions and should undergo high-resolution anoscopy regardless of the cytology result. See Video Abstract at http://links.lww.com/DCR/A654.

Author(s): Goldstone, Stephen E; Lensing, Shelly Y; Stier, Elizabeth A; Darragh, Teresa; Lee, Jeannette Y; van Zante, Annemieke; Jay, Naomi; Berry-Lawhorn, J Michael; Cranston, Ross D; Mitsuyasu, Ronald; Aboulafia, David; Palefsky, Joel M; Wilkin, Timothy | Abstract: BackgroundAnal high-grade squamous intraepithelial lesions (HSILs) ablation may reduce the incidence of invasive cancer, but few data exist on treatment efficacy and natural regression without treatment.MethodsAn open-label, randomized, multisite clinical trial of human immunodeficiency virus (HIV)-infected adults aged ≥27 years with 1-3 biopsy-proven anal HSILs (index HSILs) without prior history of HSIL treatment with infrared coagulation (IRC). Participants were randomized 1:1 to HSIL ablation with IRC (treatment) or no treatment (active monitoring [AM]). Participants were followed every 3 months with high-resolution anoscopy. Treatment participants underwent anal biopsies of suspected new or recurrent HSILs. The AM participants underwent biopsies only at month 12. The primary end point was complete clearance of index HSIL at month 12.ResultsWe randomized 120 participants. Complete index HSIL clearance occurred more frequently in the treatment group than in the AM (62% vs 30%; risk difference, 32%; 95% confidence interval [CI], 13%-48%; P l .001). Complete or partial clearance (clearance of ≥1 index HSIL) occurred more commonly in the treatment group (82% vs 47%; risk difference, 35%; 95% CI, 16%-50%; P l .001). Having a single index lesion, compared with having 2-3 lesions, was significantly associated with complete clearance (relative risk, 1.96; 95% CI, 1.22-3.10). The most common adverse events related to treatment were mild or moderate anal pain and bleeding. No serious adverse events were deemed related to treatment or study participation.ConclusionIRC ablation of anal HSILs results in more clearance of HSILs than observation alone.

Persistent infection of the anus with high-risk types of human papillomavirus (HPV) causes squamous cell carcinoma, one of the most common non-AIDS-defining cancers [1], [2]. HIV-infected individuals are at much higher risk for developing anal cancer than HIV-uninfected individuals [3], [4], [5], [6]. Approximately 70% of anal cancers are due to HPV types 16 or 18 and most genital warts are associated with HPV types 6 and 11 [7], [8]. The quadrivalent HPV (qHPV) vaccine, which induces neutralizing antibodies titers in recipients against HPV types 6, 11, 16, and 18, prevented 93% of persistent anal infections and 78% of anal squamous intraepithelial lesions caused by these types in HIV-uninfected men who have sex with men (MSM) [9]. While the qHPV vaccine series is highly immunogenic in HIV-infected adults and children, antibody titers are lower than those reported in HIV-uninfected populations [10], [11], [12]. In studies of both HIV infected and HIV-uninfected vaccine recipients, the titers developed in response to the standard three-dose qHPV series peak soon after the third dose then decline. HIV-uninfected women [13] and HIV-infected children [14] demonstrated an anamnestic response to a fourth dose of the qHPV vaccine suggesting that the qHPV vaccine induces immune memory. Published studies of HIV-infected adults receiving qHPV vaccine have relatively limited follow-up and the characteristics of the long-term humoral response have not yet been described. It is unclear how much immunity wanes in this population and whether the standard 3 dose series generates immune memory which is necessary for long-term protection against new infections. A delayed fourth vaccination can simulate antigen exposure and a robust increase in antibodies suggestive of an anamnestic response indicative of immune memory [13], [14], [15]. When exposed to specific antigens, long-lived memory immune cells generate an immune response to prevent or stop infection [13]. The AIDS Malignancy Consortium Protocol 052 (AMC052) demonstrated the safety and immunogenicity of the standard three dose qHPV vaccine series in HIV-infected adult males [10]. Here we describe the long-term titers after vaccination in this study population. Since there are no accepted criteria for an anamnestic response, we sought to describe the titers at one and four weeks after a fourth dose, similar to what has been shown in HIV-uninfected women [13]. We hypothesized that titers would be higher four weeks after a fourth dose compared with four weeks after the third dose.

Background Perianal high-grade dysplasia (Bowen disease) is traditionally treated with mapping and wide excision with possible grafting rather than local ablation. Objective The aim of this study is to examine the results of high-grade perianal dysplasia ablation. Data sources Data for this study were derived from a retrospective chart review at a surgical practice screening and treating patients for high-grade dysplasia between July 1998 and June 2013. Study selection The patients included were men who have sex with men and are undergoing perianal dysplasia ablation. Intervention Ablation of perianal dysplasia with electrocautery, laser, or infrared coagulation was performed. Main outcome measures The primary outcomes measured were the recurrence of perianal dysplasia postablation and factors affecting recurrence. Results Seventy HIV-positive and 11 HIV-negative patients enrolled; the median ages were 44.7 and 42.8 years. Median follow-up times for HIV-positive and HIV-negative patients were 4.62 and 3.53 years, and the median numbers of treatments were 4 and 1, p = 0.004. The median number of lesions treated was 1 for both groups. Only 1 HIV-negative patient had a recurrence 8 months after treatment. For HIV-positive patients, the Kaplan-Meier probability of recurrence at 1, 3, and 5 years was 38% (95% CI 26-50), 59% (95% CI 47-72), and 68% (95% CI 55-81) after the first ablation with no difference for subsequent treatments. HIV-positive patients had a relative risk of perianal high-grade squamous intraepithelial lesions of 3.72 (95% CI 2.10-6.60) compared with HIV-negative patients (p ≤ 0.0001). In multivariate analysis, only each increase in intra-anal high-grade squamous intraepithelial lesions significantly increased recurrence (HR 1.13, 95% CI 1.00-1.28, p = 0.002). Only 3 patients with perianal high-grade squamous intraepithelial lesions did not have canal dysplasia. Perianal cancer developed in 3 after being lost to follow-up. Limitations This is a retrospective analysis of 1 experienced surgeon's results. No precise way exists to accurately determine the size of the disease. Conclusions Perianal dysplasia can be successfully ablated, but recurrence remains high. Almost all patients have anal canal dysplasia. HIV-positive patients are at the greatest risk for disease and recurrence. An increased number of high-grade canal lesions increases recurrence.

Men who have sex with men have increased prevalence of both human papillomavirus and anogenital condyloma.Risk factors for multiple treatment and recurrence of anal condyloma were examined.This is a retrospective study of HIV-negative men who have sex with men who were treated for anal condyloma.This study was conducted in a private surgical practice.The patients were HIV-negative men who have sex with men, aged 18 years or older.Ablation with electrocautery or CO2 laser was performed, as well as excision and topical imiquimod condyloma treatment adjuvant.Primary clearance, defined as 4 months of condyloma-free survival posttreatment, and recurrence, defined as any anal condyloma diagnosis after primary clearance.Of 231 participants, 207 achieved primary clearance (median age, 32.0 years) and were followed (median, 18.2 months) after primary treatment. Most had intra-anal and perianal condyloma (56%), were treated with electrocautery ablation (79.2%), and required 1 treatment (range, 1-6) for clearance. There were 57 recurrences (median, 12 months). One-third each had minimal, moderate, or extensive disease. Forty-six percent of patients received imiquimod posttreatment adjuvant. High-grade dysplasia was found in 31% at presentation and 43% during follow-up. Factors associated with requiring multiple treatments for clearance were participants having moderate disease (adjusted odds ratio, 6.0 (1.7-21.4)) and receiving imiquimod adjuvant (adjusted odds ratio, 4.7 (2.0-10.6)). No single factor predicted recurrence, but those with moderate disease experienced recurrences significantly sooner (median, 25 months of follow-up).This was a retrospective chart review, it was limited to a single practice, and it excluded those who did not achieve primary clearance.Most men who have sex with men have intra-anal and perianal condyloma and concomitant high-grade dysplasia is common. Most achieved clearance with 1 treatment. Having both intra-anal and perianal condyloma, increased severity of disease, and imiquimod adjuvant were significant predictors of requiring multiple treatments for clearance. No identified risk factors proved a significant predictor of recurrence.

BACKGROUND: In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years. METHODS: A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions. RESULTS: The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively. CONCLUSION: The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community.

Objective: To determine rates of anal dysplasia in a cohort of HIV-infected men who have sex with men (MSM), women, and heterosexual men with abnormal anal cytology. Design/methods: We evaluated histologic findings in 728 HIV-infected MSM, women, and heterosexual men referred for high-resolution anoscopy (HRA) after abnormal anal cytology in a single-center cohort study. Using multivariable logistic regression, we evaluated predictors of high-grade squamous intraepithelial lesion (HSIL) histology or invasive carcinoma including age, sexual behavior, receptive anal intercourse (RAI), anogenital warts, smoking status, antiretroviral therapy, CD4+ T-cell count, and HIV-1 plasma viral load. Results: A total of 2075 HIV-positive patients were screened with anal cytology and 62% of MSM, 42% of women, and 29% of heterosexual men had abnormal findings (P

Objective: Random biopsy (RB) of normal appearing cervix during colposcopy increases high-grade dysplasia (HSIL) diagnosis but has not been studied in high-resolution anoscopy (HRA), that is, colposcopy transferred to the anal canal. We investigated the utility of RB during HRA. Design: At HRA, the anal canal was divided into 4 quadrants. Areas suspicious for HSIL had standard biopsy (SB); random biopsies were taken from quadrants without apparent HSIL. Inclusion required $1 RB. Two providers performed all procedures (S.E.G., .10 years experience; M.M.G. 3 years experience) Results: Overall, 391 participants enrolled (mean age, 44.7 years); most were male (87.2%), non-Hispanic (69.8%), white (62.7%), and HIV positive (72.9%). Of 1761 biopsies, 883 were RBs (mean, 2.26/ participant). HSIL was identified in 252 lesions, and in 132 participants (33.8%). Thirty-two HSILs (12.7%) and 13 participants (9.8%) were diagnosed by RB. RB increased total HSILs identified per participant (mean, 0.65 vs. 0.56; P , 0.001) and participants with HSIL (P , 0.001). Histologically, HSIL diagnoses via SB were no more dysplastic than random biopsies (relative risk, 0.82; range, 0.37– 1.8). In multivariable analysis, factors affecting adjusted relative risk (ARR) of HSIL with any biopsy were provider [S.E.G vs. M.M.G.; ARR, 5.9; 95% confidence interval (CI), 1.3 to 25.8] and oncogenic human papillomaviral infection (ARR, 24.3; 95% CI, 2.8 to 213.3). Risk of HSIL on RB alone in multivariate analysis was associated with HSIL via SB (ARR, 3.4; 95% CI, 1.6 to 7.1 or ARR, 1.4; 95% CI, 1.1 to 1.9 per standard HSIL). Provider, HIV status, detectable viral load, age, or prior screening for or treatment of HSIL did not affect the utility of RB. Conclusions: Addition of RB to HRA significantly increased both the number of HSILs and participants with HSIL identified.

Purpose: High-grade anal intraepithelial neoplasia (HGAIN) is the precursor lesion to invasive anal cancer. Human papillomavirus (HPV) vaccination holds great promise for preventing anal cancer. Methods: We examined 235 HIV-1-infected men screening for participation in a multisite clinical trial of a quadrivalent HPV vaccine. All participants had anal swabs obtained for HPV testing and cytology and high-resolution anoscopy with biopsies of visible lesions to assess for HGAIN. Results: HPV types 16 and 18 were detected in 23% and 10%, respectively; abnormal anal cytology was found in 56% and HGAIN in 30%. HGAIN prevalence was significantly higher in those with HPV16 detection compared to those without (38% vs 17%; P = .01). Use of antiretroviral therapy and nadir and current CD4+ cell count were not associated with abnormal anal cytology or HGAIN. Conclusion: HGAIN is highly prevalent in HIV-infected men. Further studies are needed on treatment and prevention of HGAIN.

Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at disproportionately high risk for anal cancer. There is no definitive approach to the management of high-grade squamous intraepithelial lesions (HSIL), which are precursors of anal cancer, and evidence suggests that posttreatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves HSIL treatment effectiveness. The objectives of this study were to evaluate the optimal HSIL management strategy with respect to clinical effectiveness and cost-effectiveness and to identify the optimal age for initiating HSIL management.A decision analytic model of the natural history of anal carcinoma and HSIL management strategies was constructed for HIV-positive MSM who were 27 years old or older. The model was informed by the Surveillance, Epidemiology, and End Results-Medicare database and published studies. Outcomes included the lifetime cost, life expectancy, quality-adjusted life expectancy, cumulative risk of cancer and cancer-related deaths, and cost-effectiveness from a societal perspective.Active monitoring was the most effective approach in patients 29 years or younger; thereafter, HSIL treatment plus adjuvant qHPV vaccination became most effective. When cost-effectiveness was considered (ie, an incremental cost-effectiveness ratio [ICER]$100,000/quality-adjusted life-year), do nothing was cost-effective until the age of 38 years, and HSIL treatment plus adjuvant qHPV vaccination was cost-effective beyond the age of 38 years (95% confidence interval, 34-43 years). The ICER decreased as the age at HSIL management increased. Outcomes were sensitive to the rate of HSIL regression or progression and the cost of high-resolution anoscopy and biopsy.The management of HSIL in HIV-positive MSM who are 38 years old or older with treatment plus adjuvant qHPV vaccination is likely to be cost-effective. The conservative approach of no treatment is likely to be cost-effective in younger patients. Cancer 2017;123:4709-4719. © 2017 American Cancer Society.

The hc2 human papillomavirus DNA test (HC2) is effective when screening women for cervical dysplasia, and it might be effective in the screening for anal dysplasia. Differences between the anal and the cervical canals could affect the test performance. This prospective study (n = 292) measured the HC2 signal and in agreement with a histologic endpoint of high- grade dysplasia for anal specimens collected in various ways. Sensitivities were 91%, 85%, and 62% for specimens collected in a sample transport medium and a liquid-based cytology medium processed by Gyn or Non-Gyn protocol, respectively. HC2 sensitivity and specificity to predict high-grade anal dysplasia were similar for brush or swab specimen collections, but HC2 signal was 6 times higher with the brush. Specificity and sensi- tivity were similar whether the sample was collected first or after a cytology sample for brush or swab, but swab specimens at the second collection had an HC2 signal (mean) 48% lower than that of the first collection, and the swab cellularity was lower. The presence of maximum stool decreased the HC2 signal in anal swab specimens. Consensus polymerase chain reaction (PCR) confirmed that the 13 human papillomavirus probe types in HC2 were optimal for performance. HC2 could potentially be further investigated for use in screening anal dysplasia. A larger prospective study is indicated.

Background. Most squamous cell anal cancers and precancerous lesions are attributed to human papillomavirus (HPV) infection. By preventing HPV infection, quadrivalent HPV vaccine (qHPV) reduces risk of anal cancer/precancerous lesions in young men who have sex with men (MSM) without history of anal cancer/precancerous lesions. In our practice, many persons with history of precancerous anal lesions or high-grade anal intraepithelial neoplasia (HGAIN) have been vaccinated electively. We determined whether qHPV is effective at preventing recurrence of HGAIN. Methods. This nonconcurrent cohort study evaluated 202 patients with a history of previously treated HGAIN. Eighty-eight patients were vaccinated, and 114 patients were unvaccinated. We determined the recurrence rate of histologic HGAIN in vaccinated versus unvaccinated patients. Results. During 340.4 person-years follow-up, 12 (13.6%) vaccinated patients and 35 (30.7%) unvaccinated patients developed recurrent HGAIN. Multivariable hazards ratio (HR) analysis showed testing positive for oncogenic HPV genotypes within 8 months before study entry was associated with increased risk of recurrent HGAIN at 2 years after study entry (HR 4.06; 95% confidence interval [CI], 1.58‐10.40; P 5 .004), and qHPV was associated with decreased risk of recurrent HGAIN (HR .50; 95% CI, .26‐.98; P 5 .04). Among patients infected with oncogenic HPV, qHPV was associated with decreased risk of recurrent HGAIN at 2 years after study entry (HR .47; 95% CI, .22‐1.00; P 5 .05). Conclusions. qHPV significantly reduces HGAIN recurrence among MSM and may be an effective posttreatment adjuvant form of therapy. A randomized controlled trial is needed to confirm these results.

The rate of anal cancer is increasing among both women and men, particularly men who have sex with men. Caused by infection with human papillomavirus (HPV), primarily HPV type 16 or 18, anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3). We studied the safety and efficacy of quadrivalent HPV vaccine (qHPV) against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 infection in men who have sex with men.In a substudy of a larger double-blind study, we randomly assigned 602 healthy men who have sex with men, 16 to 26 years of age, to receive either qHPV or placebo. The primary efficacy objective was prevention of anal intraepithelial neoplasia or anal cancer related to infection with HPV-6, 11, 16, or 18. Efficacy analyses were performed in intention-to-treat and per-protocol efficacy populations. The rates of adverse events were documented.Efficacy of the qHPV vaccine against anal intraepithelial neoplasia associated with HPV-6, 11, 16, or 18 was 50.3% (95% confidence interval [CI], 25.7 to 67.2) in the intention-to-treat population and 77.5% (95% CI, 39.6 to 93.3) in the per-protocol efficacy population; the corresponding efficacies against anal intraepithelial neoplasia associated with HPV of any type were 25.7% (95% CI, -1.1 to 45.6) and 54.9% (95% CI, 8.4 to 79.1), respectively. Rates of anal intraepithelial neoplasia per 100 person-years were 17.5 in the placebo group and 13.0 in the vaccine group in the intention-to-treat population and 8.9 in the placebo group and 4.0 in the vaccine group in the per-protocol efficacy population. The rate of grade 2 or 3 anal intraepithelial neoplasia related to infection with HPV-6, 11, 16, or 18 was reduced by 54.2% (95% CI, 18.0 to 75.3) in the intention-to-treat population and by 74.9% (95% CI, 8.8 to 95.4) in the per-protocol efficacy population. The corresponding risks of persistent anal infection with HPV-6, 11, 16, or 18 were reduced by 59.4% (95% CI, 43.0 to 71.4) and 94.9% (95% CI, 80.4 to 99.4), respectively. No vaccine-related serious adverse events were reported.Use of the qHPV vaccine reduced the rates of anal intraepithelial neoplasia, including of grade 2 or 3, among men who have sex with men. The vaccine had a favorable safety profile and may help to reduce the risk of anal cancer. (Funded by Merck and the National Institutes of Health; ClinicalTrials.gov number, NCT00090285.).

BACKGROUND: Ten years ago, we published findings from anal dysplasia screening in a metropolitan surgical practice where the majority of men who have sex with men had biopsy-proven high-grade anal intraepithelial neoplasia. OBJECTIVE: This study aimed to determine the effect of 10 years of experience in anal dysplasia screening on the prevalence of high-grade anal intraepithelial neoplasia. DESIGN: A retrospective chart review was performed of all anal cytology results of 1189 men who have sex with men screened in a 1-year period, with subsequent highresolution anoscopy and biopsy as necessary. PATIENTS: The patients studied were men who have sex with men. MAIN OUTCOME MEASURE: The main outcome measure was biopsy-proven high-grade anal intraepithelial neoplasia. RESULTS: There were 315 (37.2%) biopsy-verified instances of high-grade anal intraepithelial neoplasia. Regression analysis determined that age, HIV status, infection by high-risk human papillomavirus, and abnormal cytology results were significant predictors of high-grade anal intraepithelial neoplasia. In a 1-year period, the number of men who have sex with men screened was nearly 7 times greater than in the 2-year period studied 10 years earlier. LIMITATIONS: We did not separately analyze patients who had previously been treated for high-grade anal intraepithelial neoplasia. CONCLUSIONS: Severity of cytology and infection with high-risk human papillomavirus are the most significant predictors of high-grade anal intraepithelial neoplasia, underscoring the importance of anal dysplasia screening. Our ability to identify high-grade anal intraepithelial neoplasia has improved with 10 years of experience performing high-resolution anoscopy.

Background. We examined the baseline prevalence of penile, scrotal, and perineal/perianal human papillomavirus (HPV) in heterosexual men (HM). We also evaluated baseline characteristics of HM to assess factors associated with prevalent HPV detection. Methods. We tested serum samples from 3463 HM aged 16–24 years with 1–5 lifetime female sexual partners for antibodies to HPV 6, 11, 16, and 18. We collected baseline swab specimens for the detection of DNA of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 from 3 areas: penile, scrotal, and perineal/perianal. Risk factors for prevalent HPV DNA detection were evaluated. Results. The prevalence of any tested HPV type was 18.7% at the penis, 13.1% at the scrotum, 7.9% at the perineal/perianal region, and 21.0% at any site. Having .3 lifetime female sexual partners had the greatest impact on HPV prevalence: odds ratio (OR) 3.2 (95% confidence interval (CI) 2.1–4.9) for HPV 6, 11, 16, and 18; and OR 4.5 (95% CI 3.3–6.1) for all HPV types tested. HPV DNA detection was highest in Africa. Neither condom usage nor circumcision was associated with HPV DNA prevalence. Conclusion. Genital-HPV DNA detection is common in young, sexually active HM. We found HPV to be most prevalent in African men and least prevalent in men from the Asia-Pacific region. Increased numbers of sexual partners was an important risk factor for HPV DNA prevalence.

Background. We examined the baseline prevalence of penile, scrotal, perineal/perianal, and intra-anal human papillomavirus (HPV) infection in human immunodeficiency virus (HIV)‐seronegative men who have sex with men (MSM). Methods. Data were analyzed from 602 MSM aged 16‐27 years with

Background Human immunodeficiency virus type 1 (HIV-1)-infected men are at increased risk for anal cancer. Human papillomavirus (HPV) vaccination may prevent anal cancer caused by vaccine types. Methods AIDS Malignancy Consortium Protocol 052 is a single-arm, open-label, multicenter clinical trial to assess the safety and immunogenicity of the quadrivalent HPV (types 6, 11, 16, and 18) vaccine in HIV-1-infected men. Men with high-grade anal intraepithelial neoplasia or anal cancer by history or by screening cytology or histology were excluded. Men received 0.5 mL intramuscularly at entry, week 8, and week 24. The primary end points were seroconversion to vaccine types at week 28, in men who were seronegative and without anal infection with the relevant HPV type at entry, and grade 3 or higher adverse events related to vaccination. Results There were no grade 3 or greater adverse events attributable to vaccination among the 109 men who received at least 1 vaccine dose. Seroconversion was observed for all 4 types: type 6 (59 [98%] of 60), type 11 (67 [99%] of 68), type 16 (62 [100%] of 62), and type 18 (74 [95%] of 78). No adverse effects on CD4 counts and plasma HIV-1 RNA levels were observed. Conclusions The quadrivalent HPV vaccine appears safe and highly immunogenic in HIV-1-infected men. Efficacy studies in HIV-1-infected men are warranted. Clinical trials registration. NCT 00513526.

Many men who have sex with men (MSM) present with complaints of bleeding, pain, and inflammation. We endeavored to determine the incidence of sexually transmitted infections in MSM referred for treatment of these symptoms and the effect of empiric therapy.A retrospective chart review of all MSM seen in 2007 at one surgical practice diagnosed with presumptive proctitis was performed. All MSM are routinely tested for sexually transmitted infections.Twenty-six MSM were identified (mean age, 38 years), and 17 (65 percent) were HIV+. Bleeding and pain were the most common complaints seen in 19 (73 percent) and 16 (62 percent), respectively. The most common findings were discharge in 15 (58 percent) and blood in 14 (54 percent). Sexually transmitted infections were identified in 21 (86 percent) and 3 (11 percent) had unidentified etiology. Gonorrhea was found in eight (43 percent), herpes simplex virus in six (29 percent), lymphogranuloma venereum in four (19 percent), and two each (10 percent) had Chlamydia and syphilis. Three had multiple infections. All but two treated empirically responded without complication and they had Crohn's colitis (n = 1) and rectal lymphoma (n = 1).Sexually transmitted infections are a common cause of proctitis and appropriate testing is imperative. Lymphogranuloma venereum is a common cause. Empiric treatment leads to rapid resolution and diminishes the chance for spread.

The incidence of anal high-grade dysplasia in men who have sex with men is increasing. Anal cytology that shows atypical squamous cells of undetermined significance is common, nonspecific, and rarely predicts high-grade squamous intraepithelial lesion. We want to know whether Hybrid-Capture II(R) testing for oncogenic human papillomavirus (human papillomavirus+) in men who have sex with men with atypical squamous cells of undetermined significance is beneficial and whether other predictors of high-grade squamous intraepithelial lesion exist.We performed a retrospective chart review of men who have sex with men undergoing anal screening with atypical squamous cells of undetermined significance cytology, Hybrid-Capture(R) II testing, and biopsy. Records were analyzed for all screenings.A total of 597 men who have sex with men enrolled and had 1,015 atypical squamous cells of undetermined significance cytology results: 185 (18.2 percent) had high-grade squamous intraepithelial lesion and 156 (84 percent) were human papillomavirus+. The rates for sensitivity, specificity, positive predictive value, and negative predictive value were 84, 53, 29, and 94 percent, respectively. Of 390 low-grade squamous intraepithelial lesion cytology results, high-grade squamous intraepithelial lesion was found in 141 and 127 (90 percent) were human papillomavirus+. Those with previous high-grade squamous intraepithelial lesions or human immunodeficiency virus had increased risk of high-grade squamous intraepithelial lesion (hazard ratio = 2.2 and hazard ratio = 1.95, respectively). Age was not a factor.Hybrid-Capture II(R) testing is useful in men who have sex with men with atypical squamous cells of undetermined significance. Referring only those with oncogenic human papillomavirus for biopsy reduces the number requiring this by almost half but some high-grade squamous intraepithelial lesions are missed. History of high-grade squamous intraepithelial lesion and human immunodeficiency virus are predictors of high-grade squamous intraepithelial lesion while screening intervals might be lengthened absent oncogenic human papillomavirus or in those free of high-grade squamous intraepithelial lesion for long periods.

Objective: To evaluate prospectively the safety of the infrared coagulator (IRC) as a treatment for anal high-grade squamous intraepithelial lesions (HSILs) in HIV-infected individuals and to seek preliminary evidence for efficacy. Methods: HIV-infected patients with ≤ biopsy-proven internal anal HSILs received office-based treatment with the IRC at participating AIDS Malignancy Consortium sites. Treatments were performed during high-resolution anoscopy (HRA) under local anesthesia. Patients were reevaluated at 3 months, and persistent lesions could be retreated. Patients were evaluated every 3 months for a year with anal cytology and HRA with biopsy. Human papillomavirus (HPV) DNA was measured at baseline and at follow-up using MY09/MY11 L1 polymerase chain reaction. Results: A total of 44 HSILs were treated from 16 men and 2 women. HPV 16 was the most common HPV type identified. There was no consistent change in HPV type or viral load in patients before and after treatment with the IRC. No procedure-related severe adverse events were reported. Twelve patients reported mild or moderate anal/rectal pain or bleeding. Conclusions: The IRC is a well-tolerated method of treating discrete anal canal HSILs in HIV-infected patients. A larger study to characterize its efficacy better in the management of HSILs in HIV-infected individuals is warranted.

The incidence of anal squamous carcinoma in males who have sex with males is rising. We reported that infrared coagulation of high-grade squamous intraepithelial lesions in HIV-positive males who have sex with males yielded a recurrence rate after the first ablation of 65 percent and 58 percent after a second ablation. The cure rate of an individual lesion was 72 percent. We endeavored to determine whether this technique demonstrates improved results in HIV-negative males who have sex with males. We performed a retrospective review of medical records on HIV-negative males who have sex with males who had infrared coagulation ablation of anal high-grade squamous intraepithelial lesions. Patients had at least six months' follow-up with cytology, high-resolution anoscopy, and biopsy. Recurrent high-grade squamous intraepithelial lesions were retreated. Seventy-five patients were enrolled, with a median age of 36 years, and 113 lesions were treated. Forty patients (53 percent) developed a recurrence in a median time of 238 days and 35 patients (47 percent) were disease free for a median of 516 days. When patients were treated a second or third time, recurrence rates dropped to 28 and 0 percent, respectively. The probability of successfully treating an individual lesion at first infrared coagulation was 81 percent and 93 percent when retreated. HIV-positive patients were twice as likely to have lesions persist and 1.7 times more likely to develop a recurrent high-grade squamous intraepithelial lesion. No patient developed squamous-cell carcinoma, anal stenosis, or had a serious complication. Infrared coagulation is a safe and effective office-based procedure for treating anal high-grade squamous intraepithelial lesions. Although recurrence was high after the first infrared coagulation, repeated treatment led to resolution of high-grade squamous intraepithelial lesions. Treatment success with infrared coagulation is significantly superior in HIV-negative patients compared with HIV-positive patients.

The incidence of invasive anal squamous carcinoma in men who have sex with men is rising, particularly in those with human immunodeficiency virus. As in the cervix the high-grade squamous intraepithelial lesion is thought to be an invasive squamous cell carcinoma precursor. Cervical high-grade squamous intraepithelial lesions are treated by removing the squamocolumnar transition zone. This is not possible in the anus, where treatment is often surgical and is accompanied by significant pain and morbidity. Better office-based techniques to treat anal high-grade squamous intraepithelial lesions are needed. We employed the infrared coagulator™ in an office setting to ablate high-grade squamous intraepithelial lesions. A retrospective review of medical records was performed on 68 human immunodeficiency virus-positive men who have sex with men who underwent infrared coagulator™ ablation of biopsy-proven high-grade dysplasia from the time we began using the procedure in 1999. All patients have had at least six months of follow-up. Procedures were performed with local anesthesia on patients with discrete high-grade squamous intraepithelial lesions. Follow-up consisted of anal cytology with high-resolution anoscopy and biopsy of suspicious areas every three to six months. New or recurrent high-grade dysplasia was retreated. Patients with circumferential or bulky disease were treated in the operating room and were excluded from the study. Altogether, 68 patients met the enrollment criteria. The median patient age was 41 years (range 29–62 years). A total of 165 lesions were treated (mean 1.6 lesions, range 1–5) and only 46 (28 percent) persisted. However, 44 patients (65 percent) developed a new or persistent high-grade squamous intraepithelial lesion within a median time of 217 days (range 27–566 days) after infrared coagulation. The remaining 24 patients (35 percent) were free of high-grade dysplasia for a median of 413 days (range 162–1313 days) after infrared coagulation. When patients were treated a second or third time, the incidence of new or persistent high-grade dysplasia dropped to 58 percent and 40 percent, respectively. The probability of curing a retreated lesion was 72 percent. Using generalized estimating equations, the incidence of high-grade dysplasia decreased with repeated infrared coagulator™ treatments. No patient developed squamous-cell carcinoma, had a serious adverse event, or developed anal stenosis. The infrared coagulator™ is a safe, office-based modality for treating anal high-grade squamous intraepithelial lesion in human immunodeficiency virus-positive men who have sex with men. Successive treatments led to decreased recurrence rates.

PURPOSE: Human papillomavirus causes anogenital squamous intraepithelial lesions, warts, and cancer. Treatment of squamous intraepithelial lesions to prevent cancer often requires extensive surgery. We tested a human papillomavirus-specific immunotherapy, HspE7, as a potential alternative. METHODS: HspE7 was constructed by fusing heat shock protein Hsp65 from bacille Calmette-Guerin to E7 protein from human papillomavirus-16. Improvement in pathologic diagnosis of patients with persistent high-grade squamous intraepithelial lesions was studied in an open-label trial (HspE7 500 μg monthly ×3). Anogenital warts were not a trial parameter, but a retrospective review of the medical records of the first 22 patients enrolled at one site was undertaken to estimate the quality and frequency of responses of anogenital warts. Patients with warts by physical examination at baseline were scored at 24 weeks as to the percent reduction in wart size. RESULTS: Fourteen of the 22 patients had warts at baseline. At Week 24, 3 of the 14 patients had complete resolution of their warts, and 10 had warts reduced in size an estimated 70 to 95 percent. The remaining patient’s warts increased in size. The reduction in size in most patients greatly diminished the procedure necessary for complete ablation. No serious or severe adverse events were related to HspE7. CONCLUSIONS: A retrospective review of patients’ medical records suggests that HspE7 may be broadly active in anogenital warts. This activity crosses multiple human papillomavirus types. The warts improved substantially but usually did not totally disappear within six months. Patient follow-up continues. A new randomized, placebo-controlled trial is underway to evaluate these findings.

Background Colorectal surgeons are ideal referral sources to screen for and treat high-grade anal dysplasia (high-grade squamous intraepithelial lesion [HSIL]) and anal cancer. Anal cytology and high-resolution anoscopy (HRA) using acetic acid and magnification are optimal methods for screening. We endeavored to determine US colorectal surgeons’ attitudes and practices regarding HSIL screening. Methods An Internet-based survey with questions related to clinician demographics and attitudes and practices regarding anal dysplasia was sent to US members of the American Society of Colon and Rectal Surgeons. Results Of 1655 requests, 290 (18%) eligible participants responded. Most were white (83%), male (76%), board-certified colorectal surgeons (89%), and graduating medical school after 1990 (54%), almost all treated patients at risk for anal cancer and had read research on HSIL. Approximately one-third of respondents had performed anal cytology, and one-third had performed HRA. When evaluating patients for HSIL in surgery, only 31% use acetic acid with magnification. Of 99 participants who perform HRA, 46% were formally trained, 83% primarily do HRA primarily in the operating room, and 82% use acetic acid with magnification. Knowledge of HSIL risk factors was not associated with screening. Women, more recent graduates, and surgeons with higher percentages of HIV-infected patients were more likely to screen. Screening barriers included no training (52%), not a priority (23%), lack of evidence (21%), and cost (8%). Conclusions American Society of Colon and Rectal Surgeons members responding to the survey by and large do not screen for anal dysplasia. Those that do are often not formally trained and use inadequate technique.

Background The quadrivalent human papillomavirus vaccine (qHPV) is FDA-approved for use in males 9 to 26 years old to prevent anogenital condyloma. The objective of this study is to determine if qHPV is effective at preventing anal condyloma among men who have sex with men (MSM) aged 26 years and older. Methods This post-hoc analysis of a nonconcurrent cohort study evaluated 210 patients without history of anal condyloma and 103 patients with previously-treated anal condyloma recurrence-free for at least 12 months prior to vaccination/time zero. We determined the rate of anal condyloma development in vaccinated versus unvaccinated patients. Results 313 patients with mean age 42 years were followed for median 981 days. During 773.6 person-years follow-up, condyloma developed in 10 (8.6%) vaccinated patients (incidence of 3.7 per 100 person-years) and 37 (18.8%) unvaccinated patients (incidence 7.3 per 100 person-years; p = 0.05). Multivariable hazards ratio showed that qHPV was associated with decreased risk of anal condyloma development (HR 0.45; 95% CI 0.22-0.92; p = 0.03). History of anal condyloma was associated with increased risk of anal condyloma development (HR 2.28; 95% CI 1.28-4.05; p = 0.005), as was infection with oncogenic HPV (HR 3.87; 95% CI 1.66-9.03; p = 0.002). Conclusions Among MSM 26 years of age and older with and without history of anal condyloma, qHPV reduces the risk of anal condyloma development. A randomized controlled trial is needed to confirm these findings in this age group.

A small number of HPV types are related to a majority of HPV-related neoplastic lesions in humans. High-risk types such as HPV 16 and 18 are most often implicated, although other oncogenic and non-oncogenic HPV types can cause disease in men. The efficacy of the quadrivalent HPV vaccine (qHPV) against external genital lesions and intra-anal disease related to HPV in men has been demonstrated. This report examines the vaccine's efficacy against disease due to 10 additional non-vaccine HPV types, as well as efficacy regardless of HPV detection. The data presented suggest that vaccinating males against HPV 6, 11, 16 and 18 protects them against most vaccine HPV-type related anogenital disease. However, significant efficacy against disease due to non-vaccine HPV types was not seen. In addition, the data do not provide any evidence that vaccination with qHPV vaccine will increase the likelihood of disease caused by non-vaccine types in the short term.

The incidence of anal human papillomavirus (HPV) infection and of HPV-related disease in men who have sex with men continues to rise. Screening procedures can be uncomfortable and may lead to decreased patient compliance. We endeavored to determine the tolerability of screening procedures for anal HPV disease.This was a 2-visit screening study. On visit 1 (V1), cells for cytology (using a swab) and HPV testing (randomized to a brush or swab) were collected, followed by digital rectal examination and standard anoscopy. At visit 2 (V2), patients had repeated HPV sampling (brush or swab) and high-resolution anoscopy with biopsy where indicated. Patients reported discomfort of procedures (0-5) and complications.Visit 1 standard anoscopy caused the most discomfort (mean = 1.90). Visit 2 biopsy caused the least discomfort (mean = 1.04). The mean discomfort difference between V1 HPV sampling with swab (1.56) and brush (1.86) was significant (p = .03) but not at V2. The mean difference between V2 HPV brush (1.63) and V1 brush (1.86) discomfort was significant (p = .02), but there was no significant difference for V1 and V2 swab. There was no discomfort difference between standard anoscopy and high-resolution anoscopy (p = .14). All patients who reported at V1 that the discomfort would prevent them from having procedure again returned for V2. There was no significant difference in bleeding or pain after V1 for brush or swab.Screening procedures for anal HPV-related disease were well tolerated, and no single procedure or HPV sampling device reduced patient compliance.

Author(s): Stier, Elizabeth A; Goldstone, Stephen E; Einstein, Mark H; Jay, Naomi; Berry, John M; Wilkin, Timothy; Lee, Jeannette Y; Darragh, Teresa M; Da Costa, Maria; Panther, Lori; Aboulafia, David; Palefsky, Joel M | Abstract: ObjectiveTo evaluate the safety and efficacy of topical cidofovir for treatment of high-grade squamous perianal intraepithelial neoplasia (PAIN) and vulvar intraepithelial neoplasia (VIN) lesions in HIV-positive individuals.DesignPhase IIa prospective multicenter trial conducted at eight clinical sites through the AIDS Malignancy Consortium.Methods: HIV-positive patients with biopsy-proven high-grade PAIN that was at least 3 cm were enrolled. PAIN biopsy specimens were assessed for human papillomavirus (HPV) using PCR and type-specific HPV probing. Participants applied 1% topical cidofovir to PAIN and VIN (if present) for six 2-week cycles. Results were designated as complete response (CR), partial response (PR) (g50% reduction in size), stable disease, or progressive disease (PD).ResultsTwenty-four men and nine women (eight with high-grade VIN as well) were enrolled. Mean age was 44 years and mean CD4 cell count was 412 cells/μl. HPV DNA (most commonly HPV16) was detected in all pretreatment study specimens. Twenty six (79%) participants completed treatment per protocol: CR, five (15%); PR, 12 (36%), stable disease, seven (21%); PD, two (6%) (one with a superficially invasive cancer and one with new area of high-grade PAIN). Treatment was well tolerated with most common adverse events being mild to moderate affecting lesional skin: pain/burning/irritation (25 patients) and ulceration (13 patients).ConclusionTopical cidofovir had 51% efficacy in the short-term treatment of high-grade PAIN and VIN with acceptable toxicity in HIV-positive individuals. Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed.

Human papillomavirus infection causes cervical cancer, a significant portion of anal, genital and oropharyngeal cancers, genital warts and recurrent respiratory papillomatosis. In June 2006, a quadrivalent human papillomavirus-6/11/16/18 vaccine (GARDASIL/SILGARD®; Merck, NJ, USA) was licensed in the USA; subsequent approval has been granted in the EU (September 2006). It has since been approved in 121 countries with over 74 million doses distributed globally as of March 2011.

Human papillomavirus (HPV) infection can lead to significant disease in males, including anogenital warts, intraepithelial neoplasias, and several types of oral and anogenital cancers. The quadrivalent HPV (type 6/11/16/18) L1 virus-like particle (VLP) vaccine (qHPV vaccine; Gardasil) has recently been demonstrated to prevent persistent infection and associated disease related to vaccine HPV types in males. We report the overall immunogenicity results from a trial of the quadrivalent HPV vaccine in males. Overall, 3,463 heterosexual men and 602 men who had sex with men were enrolled into a randomized, placebo-controlled, double-blind safety, immunogenicity, and efficacy study. Serum samples were collected prior to vaccination at day 1 and at months 7, 24, and 36 postvaccination. Immunogenicity was evaluated with a multiplex, competitive Luminex immunoassay. Almost all subjects (97.4 to 99.2%) seroconverted for vaccine HPV types by month 7. At month 36, 88.9%, 94.0%, 97.9%, and 57.0% of subjects were still seropositive for HPV-6, -11, -16, and -18, respectively. For all vaccine HPV types, black subjects had significantly higher antibody titers at month 7 than did both Caucasian and Asian subjects. An anamnestic antibody response was seen in men seropositive before vaccination. The vaccine was highly immunogenic in males 16 to 23 years of age; responses were comparable to those observed in women. Furthermore, the immune responses were consistent with the established efficacy of the vaccine in the prevention of incident and persistent HPV infection, anogenital warts, and anal intraepithelial neoplasia.

Background Anal squamous cell carcinoma (ASCC) incidence has been rising over the past decade, most dramatically in HIV-positive men who have sex with men (MSM). We aimed to identify a novel in-office approach for ablating high-grade anal intraepithelial neoplasia (HGAIN), the believed precursor lesion to ASCC. Materials and methods We performed a retrospective analysis of medical records from a New York City surgical practice, identifying patients with HGAIN treated with electrocautery ablation (ECA) and followed for at least 5 months with high-resolution anoscopy, biopsies, and/or cytology. We sought to determine HGAIN recurrence and progression to ASCC after ECA. Results Two hundred thirty-two MSM, 132 HIV positive and 100 HIV negative, with median follow-up of 19.0 and 17.5 months, respectively, met inclusion criterion. In HIV-negative and HIV-positive MSM, the probability of curing a lesion after first ECA was 85% and 75%, respectively. Over follow-up, 53% of HIV-negative and 61% of HIV-positive patients recurred. After first and second ECA, HIV-positive MSM were 1.28 times (P = 0.16) and 2.34 times (P = 0.009) more likely to recur than HIV-negative MSM. The majority of recurrence was due to development of additional lesions at untreated sites (metachronous recurrence). One patient (0.4%) developed ASCC. At last visit, 83% of HIV-negative and 69% of HIV-positive patients were HGAIN free. Conclusions ECA is an effective treatment for HGAIN, with fewer patients progressing to ASCC than predicted with expectant management. HIV-positive patients are significantly more likely to recur than HIV-negative patients.

Hybrid Capture 2 (HC2) Human Papillomavirus (HPV) DNA Test® is FDA approved and is a proven aid in detecting HPV infections of the cervix and as an aid in diagnosing, with cytology, cervical disease. A prospective feasibility study was conducted to determine if HC2 testing has utility when screening for high-grade anal dysplasia (AIN2+). We enrolled 298 patients (45% HIV+) who had AIN2+ screening with cytology, histology and HC2 testing for two specimens: a swab into liquid-based cytology medium and either a swab or a brush collection in specimen transport medium (STM). High-resolution anoscopy was performed on all patients with biopsy of AIN2+ suspicious lesions. Cytology was benign (42%), atypical squamous cells of undetermined significance (30%), low-grade squamous intraepithelial lesion (18%), high-grade squamous intraepithelial lesion (1%), ASCUS possibly high-grade dysplasia (1.7%) and nondiagnostic (7%) and 36% had AIN2+ histology. Sensitivity and specificity for predicting AIN2+ histology for any abnormal cytology were 77 and 52%, whereas HC2 sensitivity and specificity were 91 and 40% (p = 0.005 for sensitivity), respectively. There was no significant difference in HC2 sensitivity or specificity between brush and swab or STM and residual cells from cytology. AIN2+ was found in 20% of patients with benign cytology. Only nine AIN2+ specimens were HC2−. This prospective study indicates that HC2 may be useful when screening for anal dysplasia; however, a larger study is recommended.

Prophylactic vaccination with a quadrivalent HPV (types 6, 11, 16, 18) vaccine (qHPV) has been shown to prevent infection with HPV 6/11/16/18 and associated disease in women and more recently, in men. Here we report on the safety and reactogenicity of the qHPV vaccine in males. A total of 4,065 healthy males aged 16-26 years were enrolled into a randomized, placebo-controlled, double-blind trial. Subjects were randomized 1:1 to receive qHPV vaccine or placebo at day 1, month 2, and month 6. Safety and tolerability were assessed via the collection of reported adverse experiences (AEs). All serious AEs (vaccine- or procedure-related or not) and all deaths occurring during the study were recorded. Safety analyses were conducted in all subjects who received at least one dose of vaccine or placebo. The proportion of subjects who reported at least one injection-site AE was higher in the qHPV vaccine group versus the placebo group (60.1% vs 53.7%, respectively), however most of these AEs were mild/moderate in intensity. The incidence of at least one systemic AE was comparable between the vaccine and placebo groups (31.7% vs 31.4%, respectively). There were no vaccine-related serious AEs or deaths. The occurrence of AEs did not increase with each successive injection, and among trial participants who were seropositive for at least one vaccine HPV type at enrollment, the profile of adverse events was similar to that of the entire study cohort. The qHPV vaccine was generally well tolerated in males aged 16-26 years and had a favorable safety profile.

PURPOSE:Anal cytology is used to screen patients for anal dysplasia. Anal pap smears are collected without direct visualization of the canal, whereas cervical cytology is obtained with direct visualization. Current screening guidelines dictate that patients with abnormal cytology are to be evaluated with high-resolution anoscopy, and patients with benign anal cytology forgo high-resolution anoscopy. We routinely perform standard anoscopy after cytology collection. We endeavored to determine whether our standard procedure would reveal findings supporting high-resolution anoscopy even with benign cytology. METHODS:We performed a retrospective chart review of all anal cytology results from January 2008 to March 2009, identifying the patients with benign results who had undergone high-resolution anoscopy. Records were analyzed to determine the indication for high-resolution anoscopy and biopsy results. RESULTS:We identified 2084 patients with anal cytology results, including 613 (29%) patients who had benign results and 169 (28%) patients who had undergone highresolution anoscopy. The main reasons for highresolution anoscopy were high risk of recurrent dysplasia based on prior high-grade squamous intraepithelial lesion with cytology done concurrently in 77 (46%), and abnormal anoscopy findings thought to be indicative of dysplasia (plaque or nodule suspicious of dysplasia, internal or external condyloma, dysplastic appearing fissure) in 92 (54%). Of subjects with abnormal anoscopy findings indicative of dysplasia, 25 (27%) had high-grade and 39 (42%) had low-grade dysplasia. Of those undergoing cytology and high-resolution anoscopy simultaneously, 14 (18%) had high-grade and 12 (16%) had low-grade dysplasia. In total, 90 (53%) of those with benign cytology who had high-resolution anoscopy had abnormal pathology, and 39 (23%) had high-grade dysplasia. CONCLUSIONS:Men having sex with men can have significant dysplasia with benign cytology. Standard anoscopy identifies findings indicative of dysplasia that, if present, should lead to high-resolution anoscopy even with benign cytology. Standard anoscopy should become an integral part of anal dysplasia screening. Prior recent history of high-grade dysplasia should lead to highresolution anoscopy even with benign cytology.

Background Infection with human papillomavirus (HPV) and diseases caused by HPV are common in boys and men. We report on the safety of a quadrivalent vaccine (active against HPV types 6, 11, 16, and 18) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men. Methods We enrolled 4065 healthy boys and men 16 to 26 years of age, from 18 countries in a randomized, placebo-controlled, double-blind trial. The primary efficacy objective was to show that the quadrivalent HPV vaccine reduced the incidence of external genital lesions related to HPV-6, 11, 16, or 18. Efficacy analyses were conducted in a per-protocol population, in which subjects received all three vaccinations and were negative for relevant HPV types at enrollment, and in an intention-to-treat population, in which subjects received vaccine or placebo, regardless of baseline HPV status. Results In the intention-to-treat population, 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group, for an observed efficacy of 60.2% (95% confidence interval [CI], 40.8 to 73.8); the efficacy was 65.5% (95% CI, 45.8 to 78.6) for lesions related to HPV-6, 11, 16, or 18. In the per-protocol population, efficacy against lesions related to HPV-6, 11, 16, or 18 was 90.4% (95% CI, 69.2 to 98.1). Efficacy with respect to persistent infection with HPV-6, 11, 16, or 18 and detection of related DNA at any time was 47.8% (95% CI, 36.0 to 57.6) and 27.1% (95% CI, 16.6 to 36.3), respectively, in the intention-to-treat population and 85.6% (97.5% CI, 73.4 to 92.9) and 44.7% (95% CI, 31.5 to 55.6) in the per-protocol population. Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo (57% vs. 51%, P

Prior to FDA licensure in men, a surgical practice (SG) offered the quadrivalent HPV vaccine (qHPV) off-label to men who have sex with men (MSM). We administered a written or telephone survey to MSM to elicit drivers and barriers to vaccination, sexual behavior changes post-vaccination, and knowledge. 191 subjects enrolled: 68 refused qHPV, 71 received qHPV1 year ago, and 52 received qHPV1 year ago. History of HPV infection (86%, n=164) and level of HPV and qHPV knowledge were high, with a mean of 10.8 of 13 knowledge questions correct. Ninety-seven percent of participants understood that qHPV does not cure present infection or disease. MSM refused qHPV for reasons including cost and not FDA approved; prevention of future HPV infection was the paramount driver for immunization. Vaccination did not affect sexual behavior.

It has been shown that testing for oncogenic human papillomavirus (HPV+) improves the sensitivity of cytologic diagnosis of atypical cells of undetermined significance in the cervix and anus, reducing the number of patients requiring colposcopy or high-resolution anoscopy. Some recommend that men who have sex with men with any abnormal cytology undergo high-resolution anoscopy. We endeavored to determine whether HPV testing could predict future high-grade dysplasia (high-grade squamous intraepithelial lesions) and modify screening internals.This investigation was conducted via a retrospective chart review of subjects with atypical cells of undetermined significance anal cytology, high-resolution anoscopy, and HPV testing. Records were abstracted for prior and subsequent screenings.Four hundred men who have sex with men (285 HIV-) underwent 2224 screenings. Of 224 subjects monitored for2 years, the hazard ratio for developing high-grade dysplasia was 77% less for men who have sex with men who never had oncogenic HPV (HPV-) vs those who stayed HPV+ (P.013). The hazard ratio for high-grade dysplasia in those who were HPV- vs those who became HPV- was not different. Risk of high-grade dysplasia was 28% within 6 months of becoming HPV+. The 3-year high-grade dysplasia risk was 15% and 54% for HPV- vs HPV+ subjects (P = .0006). Frequency of high-grade dysplasia in subjects who remained HPV- with predominantly atypical cells of undetermined significance cytology for 1, 2, or 3 years was 2%, 0% and 0% and was 17%, 0%, and 0% in HIV+ subjects. Kaplan-Meier analysis for HIV- subjects with HPV- predominantly atypical cells of undetermined significance cytology for 1 year showed5% incidence of high-grade dysplasia at 4 years.Change in HPV status can predict the risk of high-grade dysplasia. Subjects with predominantly HPV- atypical cells of undetermined significance cytology for 2 years have a decreased risk of high-grade dysplasia. HPV testing when screening for anal dysplasia could alter screening parameters.

In the cervix and anus, patients with atypical squamous cells of undetermined significance often do not have high-grade squamous intraepithelial lesions. In women with atypical squamous cells of undetermined significance, Hybrid-Capture II testing for oncogenic high-risk human papillomavirus is performed and those without high-risk human papillomavirus often are observed. We endeavored to determine whether Hybrid-Capture II testing would be beneficial in men who have sex with men with atypical squamous cells of undetermined significance. We performed a retrospective chart review of men who have sex with men with atypical squamous cells of undetermined significance who had high-resolution anoscopy and Hybrid-Capture II. A total of 290 men were identified (mean age, 42 years), and 212 (73 percent) were HIV-negative. High-grade squamous intraepithelial lesions were found in 50 (17 percent): 23 (10 percent) who were HIV-negative and 27 (35 percent) who were HIV-positive men. High-risk human papillomavirus was found in 138 (48 percent); 91 (43 percent) of HIV-negative and 47 (60 percent) of HIV-positive men. The sensitivity, specificity, positive predictive value, and negative predictive value of atypical cells of undetermined significance cytology combined with Hybrid-Capture II were 84, 60, 30, and 95 percent, respectively. There was no significant difference between all men vs. those who were HIV-positive or HIV-negative except for the positive predictive value. Hybrid-Capture II testing for high-risk human papillomavirus in men who have sex with men with atypical cells of undetermined significance and referring only those with high-risk human papillomavirus reduces the number who require high-resolution anoscopy by more than half. Five percent with high-grade squamous intraepithelial lesions would be missed.