Anal High-grade Squamous Intraepithelial Lesions Research Articles

Prevalence of anal HPV infection and anal HSIL among MSM 50 years and older living with or without HIV

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

Anal dysplasia and anal cancer screening practices among liver transplant centers in the United States: Results of an online survey.

Solid organ transplant recipients are at an increased risk for anogenital Human Papillomavirus (HPV)-related disease, including anal high-grade squamous intraepithelial lesions (HSIL) and anal squamous cell cancer (ASCC). Guidelines for ASCC screening in transplant recipients are limited. Our aim was to understand current practice of ASCC screening in adult liver transplant (LT) candidates and recipients at transplant centers across the United States. We surveyed medical directors of 113 LT centers across the United States which had publicly available contact information. The survey evaluated center perceptions on cancer and HPV disease risk in transplant populations, ASCC screening, barriers and facilitators for ASCC screening and HPV vaccination practices. We received 26/113 (23%) responses, of which 24 were complete and included in the analysis. Eleven of 24 (46%) centers reported screening for ASCC and 3/24 (12.5%) centers reported having formal guidelines. Centers who perform ASCC screening were more likely to perform transplants in people living with HIV and were more aware of the burden of HPV disease in transplant populations. All respondents believed that additional data on the impact of screening on ASCC incidence would support screening decisions. Increased access to specialists for screening/high-resolution anoscopy was also perceived as a facilitator. Only 7/24 (29%) centers regularly evaluated HPV vaccination status of their patients. This national survey of LT centers reveals non-standardized ASCC screening practices, and identified data, educational and resource needs to improve prevention of ASCC in this population.

Prevalence and incidence of anal high-grade squamous intraepithelial lesions in a cohort of cisgender men and transgender women who have sex with men diagnosed and treated during acute HIV acquisition in Bangkok, Thailand.

Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits. A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48). With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.

Distinct anal microbiome is correlated with anal cancer precursors in men who have sex with men living with HIV.

Anal cancer risk is elevated in men who have sex with men living with HIV (MSMLWH). Anal high-risk human papillomavirus (hr-HPV) infection is necessary but insufficient to develop high-grade squamous intraepithelial lesion (HSIL), the anal cancer precursor, suggesting additional factors. We sought to determine whether the microbiome of the anal canal is distinct by comparing it with the microbiome of stool. We also sought to determine whether changes in the anal microbiome are associated with HSIL among MSMLWH. Cross-sectional comparison of the microbiome of the anal canal with the microbiome of stool in MSMLWH and cross-sectional comparison of the anal microbiome of MSMLWH with anal HSIL with the anal microbiome of MSMLWH without anal HSIL. Sterile swabs were used to sample the anus of MSMLWH for microbiome and HPV testing, followed by high-resolution anoscopy. Stool samples were mailed from home. 16S sequencing was used for bacterial identification. Measures of alpha diversity, beta diversity and differential abundance analysis were used to compare samples. 166 anal samples and 103 matching stool samples were sequenced. Beta diversity showed clustering of stool and anal samples. Of hr-HPV-positive MSMLWH, 31 had HSIL and 13 had no SIL. Comparison of the microbiome between these revealed 28 different species. The highest-fold enrichment among MSMLWH/hr-HPV/HSIL included pro-inflammatory and carcinogenic Prevotella, Parasuterella, Hungatella, Sneathia and Fusobacterium species. The anti-inflammatory Anaerostipes caccae showed the greatest reduction among MSMLWH/hr-HPV/HSIL. The anal microbiome is distinct from stool. A pro-inflammatory and carcinogenic environment may be associated with anal HSIL.

Assessing the Potential of HPV16 E6 Seroprevalence as a Biomarker for Anal Dysplasia and Cancer Screening-A Systematic Review and Meta-Analysis.

Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex with men (MSM) living with HIV underscore the need for effective screening. While high-resolution anoscopy-guided biopsy is the gold standard, limited provider availability poses a challenge. This has spurred interest in identifying biomarkers for improved AC prevention. Antibodies against HPV16 oncoprotein E6, known as markers for cervical and oropharyngeal cancers, are the focus of the current study. The systematic review and meta-analysis included six studies meeting inclusion criteria, assessing HPV16 E6 seroprevalence in individuals with anal HSIL or AC. A two-step meta-analysis estimated pooled odds ratios and 95% confidence intervals (CI) for HPV16 E6 seroprevalence and HSIL or AC. Pooled prevalence, sensitivity, specificity, and diagnostic odds ratios were also calculated. This meta-analysis revealed a 3.6-fold increased risk of HSIL for HPV16 E6 seropositive individuals, escalating to a 26.1-fold risk increase for AC. Pooled specificity and sensitivity indicated a high specificity (0.99; 95%CI: 0.99, 0.99) but lower sensitivity (0.19; 95%CI: 0.10, 0.34) for HPV16 E6 serostatus as an AC biomarker. In conclusion, while HPV16 E6 seroprevalence demonstrates specificity as a potential biomarker for HPV-related AC, its utility as a standalone screening tool may be limited. Instead, it could serve effectively as a confirmation test, particularly in high-risk populations, alongside other diagnostic methods. Further research is imperative to explore HPV16 E6 seroconversion dynamics and alternative screening algorithms.

Effectiveness of trichloroacetic acid versus electrocautery for the treatment of anal high-grade squamous intraepithelial lesions in persons with HIV

Purpose This study aimed to compare trichloroacetic acid (TCA) versus electrocautery (ECA) for the treatment of anal high-grade squamous intraepithelial lesions (HSIL). Methods This is an observational, single-center study. All subjects with HIV who had anal HSIL treated with TCA or ECA from 2010 to 2022 were included. Effectiveness was evaluated by on-treatment analysis, defining response as the resolution of HSIL and recurrence as a new diagnosis of HSILs during follow-up. A propensity score analysis was used to adjust for confounding factors. Results In total, 227 and 260 HSIL episodes were treated with ECA and TCA, respectively. Response was observed in 61.7% (95% CI: 55.3–68) of cases treated with ECA and in 73.1% (95% CI: 67.8–78.5) with TCA (p = .004). The effectiveness of TCA was higher in large and multifocal HSILs. Side effects were common with both treatments, but no serious events were described. Tolerability was good in 77.1% and 80.7% of patients treated with ECA and TCA, respectively. At 24 months, recurrent HSIL were observed in 36.3% (95% CI: 27.3–45) and 28% (95% CI: 20.2–35.8) in the ECA and TCA groups (p = .049). A nadir CD4 cell count ≤200 cells/µl was found to be a risk factor for recurrence (OR: 1.77; 95% CI: 1.12–2.78). Conclusions In this study, treatment with TCA showed high effectiveness, low recurrence and good tolerability. Considering the benefits of TCA, it could be considered one of the first-line treatments for anal HSIL.

A phase I study of intra-anal artesunate (suppositories) to treat anal high-grade squamous intraepithelial lesions

Background Ablation or surgical excision is the typical treatment of anal high-grade squamous intraepithelial lesions (HSIL). Recurrences are common due to the persistence of underlying human papillomavirus (HPV) infection. Additional well-tolerated and effective non-surgical options for HPV-associated anal disease are needed. Methods This 3+3 dose escalation Phase I clinical trial evaluated the safety and tolerability of artesunate suppositories in the treatment of patients with biopsy-proven HSIL. Results The maximal tolerated dose was 400 mg, administered in 3 cycles. All adverse events associated with the use 200- and 400-mg artesunate suppositories were Grade 1. At the 600-mg dose, patients experienced clinically significant nausea. Conclusion Artesunate suppositories are a safe treatment option for anal HSIL.

Association of tobacco use and the presence of anal warts in people who attend the anal Neoplasia clinic in Puerto Rico

BackgroundLimited research exists regarding the association between smoking and anal warts. In this study, we evaluated this association among a clinic-based Hispanic population in Puerto Rico. MethodsCross-sectional study among eligible patients seen at the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center (2016–2023) (n = 920). Sociodemographic and clinical variables were collected from medical records. Patients underwent a high-resolution anoscopy (HRA) during the clinical visit; physicians assessed anal condylomas on HRA. Poisson regression models with robust standard errors were used to evaluate the association between smoking and anal warts. Demographic and clinical factors were also assessed. ResultsThe mean age of participants was 45.8 ± 13.1 years, 66.4 % were men, and 21.6 % were current smokers. While 10.8 % self-reported a history of anogenital condylomas, 18.9 % had anal condylomas on clinical evaluation. A higher prevalence of anal condylomas was observed among current smokers (PR = 1.28, 95 % CI: 0.94–1.75) in comparison to non-smokers in adjusted analysis, but this was not statistically significant. However, a higher prevalence of anal condylomas was observed among younger individuals (PR = 0.96, 95 % CI: 0.96–0.98) and individuals with anal high-grade squamous intraepithelial lesions (HSIL) as compared to those with benign histology (PR = 1.74. 95 % CI: 1.09–2.77). ConclusionsAlthough current smoking seemed to be positively associated with anal condylomas in this high-risk Hispanic population, this finding was not statistically significant as the power to detect an association was limited. However, younger age and HSIL diagnosis were associated with a higher prevalence of anal condylomas.

Cumulative detection of anal high-grade squamous intraepithelial lesions over two-year follow-up in men who have sex with men living with HIV in France.

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSIL) in men who have sex with men living with HIV who underwent three visits over two years, with cytology and high-resolution anoscopy (HRA), within the ANRS-EP57-APACHES study. Cumulative HSIL detection was 33% (134/410), of which 48% were detected at baseline. HSIL detection varied considerably by center (13-51%). Strongest HSIL determinants were baseline HPV16 (adjusted odds ratio [aOR] 8.2; 95% confidence interval [95%CI] 3.6-18.9), and p16/Ki67 (aOR 4.6; 95%CI 2.3-9.1). Repeat annual cytology and HRA improved HSIL detection but did not fully compensate between-center heterogeneity.

Two-Year Incidence and Cumulative Risk and Predictors of Anal High-Grade Squamous Intraepithelial Lesions (Anal Precancer) Among Women With Human Immunodeficiency Virus.

Detection and treatment of anal histologic high-grade squamous intraepithelial lesions (hHSIL) prevents anal cancer. However, anal hHSIL incidence among women with human immunodeficiency virus (HIV, WHIV) remains unknown. Performance of anal high-risk human papillomavirus ([hr]HPV), anal cytology (anal-cyt), and both for hHSIL detection longitudinally over 2 years also remains undetermined. We determined 2-year incidence and cumulative risk estimates (2-y-CR) of anal hHSIL among WHIV using prevalence and incidence (per 100 person-years [py]) observations stratified by baseline hrHPV and/or anal-cyt results. In total, 229 WHIV with complete baseline data were included in the analysis; 114 women without prevalent anal hHSIL were followed with 2 annual evaluations. Median age was 51, 63% were Black, and 23% were Hispanic. Anal hrHPV or abnormal anal-cyt was associated with an increased risk of incident anal hHSIL at 2 years (18.9/100py [95% confidence interval {CI} 11.4-31.3] and 13.4/100py [95% CI 8.0-22.7], respectively) compared with no detection of anal HPV or negative cytology (2.8/100py [95% CI 1.1-7.4] and 4.2 [95% CI, 1.8-10.2]) The presence of anal hrHPV with abnormal cytology was associated with 2-y-CR of anal hHSIL of 65.6% (95% CI 55.4%-75%); negative hrHPV with negative cytology was associated with 2-y-CR of anal hHSIL of 9.2% (95% CI 7.0-16.0). Detection of anal hrHPV or abnormal anal cytology are comparable predictors for 2-y-CR of anal hHSIL. The absence of anal hrHPV combined with negative cytology was predictive of a lower (but measurable) risk of developing anal hHSIL. These findings provide important data to inform anal cancer screening guidelines for WHIV.

Human papillomavirus vaccination and anal high-grade precancerous lesions and cancer-a real-world effectiveness study.

Human papillomavirus (HPV) vaccination has shown high efficacy against anal HPV infection and lesions in clinical trials, and the HPV prevalence and type distribution in anal precancers and cancer predict a high preventable potential for HPV vaccination. However, the real-world effectiveness of HPV vaccination against anal high-grade lesions and cancer is yet to be shown. We investigated HPV vaccine effectiveness against anal high-grade squamous intraepithelial lesion (HSIL) or worse in a nationwide cohort including all Danish women aged 17-32 years during October 2006 to December 2021 (n = 968 881). HPV vaccinations and first occurrence of anal HSIL or worse were retrieved from nationwide registries. Women were considered vaccinated after first dose and classified by age at vaccination. Using Cox regression, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for anal HSIL or worse according to vaccination status. During follow-up, the number of incident histological anal HSIL or worse cases was 37 in unvaccinated women, and less than 5 and 26 in women vaccinated at ages younger than 17 years and 17-32 years, respectively. The overall number of cancers was less than 5. Compared with unvaccinated women, the risk of histological anal HSIL or worse was reduced for women vaccinated at age younger than 17 years (HR = 0.30, 95% CI = 0.10 to 0.87). For women vaccinated at age 17-32 years, the hazard rate of anal HSIL or worse was 1.21 (95% CI = 0.73 to 2.03). This is the first study to demonstrate that HPV vaccination at a younger age is associated with substantially reduced risk of anal HSIL or worse in the general population.

High Specificity of HPV Cell-Free DNA Tests in Persons With HIV for the Detection of HPV-Related Cancer.

Persons with HIV (PWH) experience high rates of human papillomavirus (HPV)-associated cancers compared with the general population. Plasma HPV cell-free DNA (cfDNA) tests are sensitive in patients with known HPV-associated cancers. It is not known whether these tests can screen for invasive cancers in populations with high burdens of nonmalignant HPV disease such as PWH. It was not known whether HPV infection and/or noninvasive anal high-grade squamous intraepithelial lesions (HSIL) alone in this population would result in detectable HPV cfDNA, which would result in a high number of false positives if HPV cfDNA is used to screen for invasive cancers. We conducted a prospective study of PWH in 2 cohorts: 20 without anal HSIL and 20 with anal HSIL. We tested anal and vaginal swabs for HPV infection, and HPV genotyped the biopsies of anal HSIL. Finally, we performed HPV cfDNA droplet digital polymerase chain reaction to test for HPV16/18/33 from plasma samples. In the combined cohorts, the median age was 56 years, 12.5% were cisgender women, and none had detectable HIV. In total, 84.6% had prevalent anovaginal HPV infection, including 10 participants with HPV16, 13 with HPV18, and 2 with HPV33 infections. Five and 2 participants had HPV16 and HPV33 detected in anal HSIL, respectively. Despite the high prevalence of HPV infection and anal HSIL, no participant had HPV16/18/33 detectable cfDNA by droplet digital polymerase chain reaction. These results provide a strong rationale for investigating the use of HPV cfDNA in a screening setting for suspected HPV-related invasive cancers in PWH.

Cumulative incidence of anal cancer since HIV or AIDS diagnosis in the United States.

Treatment of screen-detected anal high-grade squamous intraepithelial lesions has been shown to effectively reduce the incidence of invasive anal cancer in people with HIV. We provide population-based estimates of cumulative incidence of anal cancer by risk group and age at HIV or AIDS diagnosis. The 0- to 10-year cumulative incidence of anal cancer for men who have sex with men and are younger than 30years of age at HIV diagnosis was 0.17% (95% confidence interval [CI] = 0.13% to 0.20%) compared with 0.04% (95% CI = 0.02% to 0.06%) in other men and 0.03% (95% CI = 0.01% to 0.04%) in women. For men who have sex with men and have a diagnosis of AIDS and are younger than 30years of age, the 0- to 10-year cumulative incidence was 0.35% (95% CI = 0.28% to 0.41%). Among people with HIV, men who have sex with men are at the greatest risk of anal cancer, and those with a diagnosis of AIDS had higher risk than those without AIDS. These estimates may inform recommendations for priority populations that could benefit most from anal cancer screening and treatment.

Evaluating the performance of anal cytology and high-risk HPV genotyping for detecting anal HSIL in a clinic-based sample of people living with and without HIV in Puerto Rico.

Given the disproportionately elevated anal cancer risk in high-risk populations, it is important to assess the performance of commonly used anal cancer screening tools to improve the effectiveness of detection and treatment methods. This study evaluates 1) the concordance between anal cytology and histology results and 2) the performance of cytology and high-risk human papillomavirus (HR-HPV) genotyping as screening tools for detecting histologically confirmed anal high-grade squamous intraepithelial lesions (HSIL). Data from the Anal Neoplasia Clinic in Puerto Rico (2014-2021; n = 466) was used. The clinical performance of anal cytology and HR-HPV genotyping to detect HSIL was compared to the gold standard: high-resolution anoscopy-guided biopsy. Sensitivity, specificity, positive predictive value, negative predictive value, and κ coefficients were calculated. A total of 66.95% of the patients were men, 74.0% were people living with HIV, 76.2% had anal HR-HPV infection, and 40.34% had histologically confirmed anal HSIL. The weighted κ statistic between the tests (cytology and histology) was 0.25 (p < .001). The sensitivity and specificity of cytology alone to detect anal HSIL were 84.3% (95% confidence interval [CI], 78.3%-89.1%) and 36.0% (95% CI, 30.3%-42.0%), respectively. Anal HR-HPV genotyping had higher sensitivity (92.2%; 95% CI, 87.4%-95.6%) and similar specificity (34.8%; 95% CI, 29.2%-40.7%) compared to cytology. The two tests combined (positive results following cytology or HR-HPV test) improved sensitivity to detect anal HSIL (97.9%; 95% CI, 94.8%-99.4%), but specificity was compromised (19.2%; 95% CI, 14.7%-24.4%). Although HR-HPV genotyping improved the detection of anal HSIL, HR-HPV testing had lower specificity than anal cytology alone.

Care cascade of anal dysplasia screening among MSM living with HIV from a single-center outpatient clinic.

e18607 Background: Anal cancer is the fourth most common cancer among people living with HIV with an incidence estimated to be 89 per 100,000 among men living with HIV who have sex with men (MSM). In comparison, the incidence of anal cancer in the general population is 1.6 per 100,000. The ANCHOR study which was a randomized control trial found that treating anal high-grade squamous intraepithelial lesions (HSIL) reduces the incidence of anal cancer by more than half. These findings provide a rationale for screening for anal dysplasia in people with HIV and could have an impact on recommendations for screening and treatment. The study also highlights the need for effective strategies to improve the screening and treatment of anal HSIL and providers trained in high-resolution anoscopy (HRA). Our goal was to determine the rate of screening for anal dysplasia among men who have sex with men (MSM) living with HIV attending our clinic and subsequent referral for HRA and completion of HRA in case of abnormal results. Methods: We assessed the rate of screening for anal dysplasia among the patients identifying as MSM (n = 305) at a large HIV clinic in Brooklyn, New York. An anal dysplasia care cascade was completed. The number of patients screened for anal dysplasia and the results of the screening were obtained from the EMR. All patients with results of Atypical Squamous cell of undetermined significance (ASCUS), Low-grade intra-epithelial neoplasia (LSIL), or High-grade intra-epithelial neoplasia (HSIL) on anal cytology were evaluated for evidence of referral for HRA and the number who completed the HRA was included in the descriptive analysis. Results: 60% of the total eligible patients included in the study were screened by anal cytology, 72% of those with abnormal cytology were referred for HRA and 37% completed the anoscopy (table 1). The patients in the age group 20-40 years were more likely to be screened. The number of patients with HSIL was low. Conclusions: The engagement of MSM clients in anal dysplasia screening and management was low based on our care cascade. Considering the results of our study, we aim to identify the barriers to screening as well as to referral and completion of HRA among MSM living with HIV in our patient population. [Table: see text]

Demonstrating a Statistically Significant Association Between Anal High-Grade Squamous Intraepithelial Lesion and Positive OncoE6 Anal Test in Men Who Have Sex With Men and Are Living With HIV.

The aim of the study is to determine whether a positive OncoE6 Anal Test result has statistically significant higher odds of being associated with high-grade squamous intraepithelial lesion (HSIL) and to calculate sensitivity and specificity of this test for predicting HSIL in adult men who have sex with men and are living with HIV (MSMLWH). Men living with HIV 18 years or older having ≥atypical squamous cells of undetermined significance-grade anal cytology results were eligible to enroll in this cross-sectional study. Anal samples were collected just before the high-resolution anoscopy procedure. OncoE6 Anal Test results were compared with histology, the reference standard. Sensitivity, specificity, and odds ratio were calculated using HSIL as the threshold. Two hundred seventy-seven consented MSMLWH were enrolled between June 2017 and January 2022. Of these, 219 (79.1%) had biopsies obtained and histology performed; 81 of 219 participants (37%) had 1 or more biopsies with HSIL results while the remaining 138 of 219 (63%) had only low-grade squamous intraepithelial lesion or were negative for dysplasia. Anal samples from 7 participants (8.6%, 7/81) with HSIL and 3 (2.2%, 3/138) with low-grade squamous intraepithelial lesion had positive OncoE6 Anal Test results. Odds of having HSIL were 4.26 times higher among participants testing positive for HPV16/HPV18 E6 oncoprotein(s) (OR = 4.26, 95% CI = 1.07-16.95, p = .04). The OncoE6 Anal Test demonstrated excellent specificity, 97.83% (93.78-99.55), but poor sensitivity, 8.64% (3.55-17.0). In this highest-risk population for anal cancer, one could combine the OncoE6 Anal Test, having excellent specificity, with the anal Pap test, having higher sensitivity. Patients found having both an abnormal anal Pap and positive OncoE6 Anal Test result could be triaged for rapid scheduling of their high-resolution anoscopy.

Effectiveness of topical cidofovir for treatment of refractory anal high-grade squamous intraepithelial lesion.

Ablative electrocautery is effective treating anal high-grade squamous intraepithelial lesions (HSILs). However, persistence or recurrence of the HSIL despite ablative sessions is not uncommon. The aim of this study is to assess the feasibility of topical cidofovir as salvage therapy for the management of refractory HSIL. A prospective uncontrolled unicenter study of men and transgender people who have sex with men with HIV who had a refractory intra-anal HSIL after ablative treatments and who received topical cidofovir (ointment at 1%, auto-applicated, three times a week, a total of 8 weeks) as salvage therapy. Effectiveness was evaluated on-treatment defining response as resolution or regression to low-grade lesion of HSIL in the biopsy posttreatment. Tolerance and recurrences were recorded. From 2017 to 2022, 23 patients with refractory intra-anal HSIL (78.3% persistent lesions, 39% affecting > 50% of circumference, and a median of six previous ablative sessions) were treated with topical cidofovir. A response was observed in 16 of 23 patients [69.5% (95% confidence interval (95% CI) 50.8-88.4)]. Local tolerance was reported as regular or bad in 13 patients (52.2%), requiring modification of the treatment in eight patients (three early discontinuation and five dose reduction). Non-serious side effects were reported. After a median follow-up of 30.3 months, two of the 16 patients with a response developed recurrent HSIL [recurrence rate, 25.4% at 12 months (95% CI, 0-35)]. Topical cidofovir could be a good option in the management of anal HSIL due to its good effectiveness, low recurrence rate, and acceptable tolerance even in difficult-to-treat lesions.

HPV Type Distribution in Benign, High-Grade Squamous Intraepithelial Lesions and Squamous Cell Cancers of the Anus by HIV Status.

The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, few studies have described the distribution of HR HPV genotypes other than HPV 16 in the anus of PLWH. HPV genotyping was performed by DNA amplification followed by dot-blot hybridization to identify the HR and low-risk (LR) genotypes in benign anal lesions (n = 34), HSIL (n = 30), and SCC (n = 51) of PLWH and HIV-negative individuals. HPV 16 was the most prominent HR HPV identified, but it was less common in HSIL and SCC from PLWH compared with HIV-negative individuals, and other non-HPV 16 HR HPV (non-16 HR HPV) types were more prevalent in samples from PLWH. A higher proportion of clinically normal tissues from PLWH were positive for one or more HPV genotypes. Multiple HPV infection was a hallmark feature for all tissues (benign, HSIL, SCC) of PLWH. These results indicate that the development of anal screening approaches based on HPV DNA testing need to include non-16 HR HPVs along with HPV 16, especially for PLWH. Along with anal cytology, these updated screening approaches may help to identify and prevent anal disease progression in PLWH.

Cost-effectiveness of screening and treating anal pre-cancerous lesions among gay, bisexual and other men who have sex with men living with HIV

Gay, bisexual and other men who have sex with men (GBM) living with HIV have a substantially elevated risk of anal cancer (85 cases per 100,000 person-years vs 1-2 cases per 100,000 person-years in the general population). The precursor to anal cancer is high-grade squamous intraepithelial lesion (HSIL). Findings regarding the cost-effectiveness of HSIL screening and treatment in GBM are conflicting. Using recent data on HSIL natural history and treatment effectiveness, we aimed to improve upon earlier models. We developed a Markov cohort model populated using observational study data and published literature. Our study population was GBM living with HIV aged ≥35 years. We used a lifetime horizon and framed our model on the Australian healthcare perspective. The intervention was anal HSIL screening and treatment. Our primary outcome was the incremental cost-effectiveness ratio (ICER) as cost per quality-adjusted life-year (QALY) gained. Anal cancer incidence was estimated to decline by 44-70% following implementation of annual HSIL screening and treatment. However, for the most cost-effective screening method assessed, the ICER relative to current practice, Australian Dollar (AUD) 135,800 per QALY gained, remained higher than Australia's commonly accepted willingness-to-pay threshold of AUD 50,000 per QALY gained. In probabilistic sensitivity analyses, HSIL screening and treatment had a 20% probability of being cost-effective. When the sensitivity and specificity of HSIL screening were enhanced beyond the limits of current technology, without an increase in the cost of screening, ICERs improved but were still not cost-effective. Cost-effectiveness was achieved with a screening test that had 95% sensitivity, 95% specificity, and cost≤AUD 24 per test. Establishing highly sensitive and highly specific HSIL screening methods that cost less than currently available techniques remains a research priority. No specific funding was received for this analysis.

Performance of Human Papillomavirus Attribution Algorithms to Predict Causative Genotypes in Anal High-Grade Lesions.

Gay and bisexual men (GBM) are at increased risk of human papillomavirus (HPV)-associated anal high-grade squamous intraepithelial lesions (HSILs). Understanding the fractions of HSILs attributable to HPV genotypes is important to inform potential impacts of screening and vaccination strategies. However, multiple infections are common, making attribution of causative types difficult. Algorithms developed for predicting HSIL-causative genotype fractions have never been compared with a reference standard in GBM. Samples were from the Study of the Prevention of Anal Cancer. Baseline HPV genotypes detected in anal swab samples (160 participants) were compared with HPV genotypes in anal HSILs (222 lesions) determined by laser capture microdissection (LCM). Five algorithms were compared: proportional, hierarchical, maximum, minimum, and maximum likelihood estimation. All algorithms predicted HPV-16 as the most common HSIL-causative genotype, and proportions differed from LCM detection (37.8%) by algorithm (with differences of -6.1%, +20.9%, -20.4%, +2.9%, and +2.2% respectively). Fractions predicted using the proportional method showed a strong positive correlation with LCM, overall (R = 0.73 and P = .002), and by human immunodeficiency virus (HIV) status (HIV positive, R = 0.74 and P = .001; HIV-negative, R = 0.68 and P = .005). Algorithms produced a range of inaccurate estimates of HSIL attribution, with the proportional algorithm performing best. The high occurrence of multiple HPV infections means that these algorithms may be of limited use in GBM.