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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: 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.

BackgroundMen 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.MethodsTwo 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.ResultsAmong 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.Conclusions18-26-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.

BackgroundWomen living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity.MethodsTwo hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL.ResultsThe performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology.ConclusionsXpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.

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.

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) (>50% 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.

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. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity. Methods: Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL. Results: The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology. Conclusions: Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH. [ABSTRACT FROM AUTHOR]

It is well established that persons living with HIV (PLWH) have highly elevated rates of anal HSIL and anal cancer compared with those who are not living with HIV. The 5-year risk of anal cancer following anal HSIL has been reported to be as high as 14.1% among PLWH compared with 3.2% among those who are not living with HIV. To address these concerns, the AIDS Malignancy Consortium completed a large-scale, randomized trial to compare strategies for the prevention of anal cancer among PLWH with anal HSIL. The objective of the study was to determine whether treating anal HSIL was effective in reducing the incidence of anal cancer in PLWH compared with active monitoring. This paper describes the design of the ANal Cancer/HSIL Outcomes Research Study (ANCHOR) with respect to estimating the anal cancer event rate in this high risk population. [ABSTRACT FROM AUTHOR]