Search

Background: People living with HIV (PLWH) have substantially increased incidence of anal precancer and cancer. There are very little data regarding genomic disturbances in anal precancers among PLWH. In this study, specific chromosomal variants were identified in anal squamous intraepithelial lesions., Methods: Overall, 63 anal biopsy specimens (27 low-grade intraepithelial lesions [LSIL] and 36 high-grade intraepithelial lesions [HSIL]) were collected from PLWH obtained as part of anal cancer screening in our NYC-based health system. Data on patient demographics, anal cytological, and high-risk human papillomavirus (HR-HPV) diagnoses were collected. Specimens were tested for a panel of chromosomal alterations associated with HPV-induced oncogenesis using fluorescence in situ hybridization, and analyses compared the associations of these alterations with clinical characteristics., Results: Gains of 3q26, 5p15, 20q13, and cen7 were detected in 42%, 31%, 31%, and 19% of HSIL compared with 7%, 0%, 4%, and 0% of LSIL, respectively. If at least 1 abnormality was observed, 89% had a 3q26 gain. In lesions with 5p15 gains, 20q13 gains co-occurred in 91% of cases, while cen7 gain only co-occurred with the other 3 alterations. The sensitivity and specificity of any alteration to predict HSIL were 47% (95% CI: 30%-65%) and 93% (95% CI: 76%-99%), respectively., Conclusions: Genomic alterations seen in HPV-associated cancers may help distinguish anal LSIL from HSIL. 3q26 amplification may be an early component of anal carcinogenesis, preceding 5p16, 20q13, and/or chr7., Impact: Insights into potential genomic biomarkers for discriminating high-risk anal precancers are shared., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Anal cancer incidence is significantly higher in people living with HIV as HIV increases the oncogenic potential of human papillomavirus. The incidence of anal cancer in the United States has recently increased, with diagnosis and treatment hampered by high loss-to-follow-up rates. Novel methods for the automated, real-time diagnosis of AIN 2+ could enable "see and treat" strategies, reducing loss-to-follow-up rates. A previous retrospective study demonstrated that the accuracy of a high-resolution microendoscope (HRME) coupled with a deep learning model was comparable to expert clinical impression for diagnosis of AIN 2+ (sensitivity 0.92 [P = 0.68] and specificity 0.60 [P = 0.48]). However, motion artifacts and noise led to many images failing quality control (17%). Here, we present a high frame rate HRME (HF-HRME) with improved image quality, deployed in the clinic alongside a deep learning model and evaluated prospectively for detection of AIN 2+ in real-time. The HF-HRME reduced the fraction of images failing quality control to 4.6% by employing a high frame rate camera that enhances contrast and limits motion artifacts. The HF-HRME outperformed the previous HRME (P < 0.001) and clinical impression (P < 0.0001) in the detection of histopathologically confirmed AIN 2+ with a sensitivity of 0.91 and specificity of 0.87., (© 2023. The Author(s).)

Introduction: In the United States, the effectiveness of anal cancer screening programs has been limited by a lack of trained professionals proficient in high-resolution anoscopy (HRA) and a high patient lost-to-follow-up rate between diagnosis and treatment. Simplifying anal intraepithelial neoplasia grade 2 or more severe (AIN 2+) detection could radically improve the access and efficiency of anal cancer prevention. Novel optical imaging providing point-of-care diagnoses could substantially improve existing HRA and histology-based diagnosis. This work aims to demonstrate the potential of high-resolution microendoscopy (HRME) coupled with a novel machine learning algorithm for the automated, in vivo diagnosis of anal precancer., Methods: The HRME, a fiber-optic fluorescence microscope, was used to capture real-time images of anal squamous epithelial nuclei. Nuclear staining is achieved using 0.01% wt/vol proflavine, a topical contrast agent. HRME images were analyzed by a multitask deep learning network (MTN) that computed the probability of AIN 2+ for each HRME image., Results: The study accrued data from 77 people living with HIV. The MTN achieved an area under the receiver operating curve of 0.84 for detection of AIN 2+. At the AIN 2+ probability cutoff of 0.212, the MTN achieved comparable performance to expert HRA impression with a sensitivity of 0.92 ( P = 0.68) and specificity of 0.60 ( P = 0.48) when using histopathology as the gold standard., Discussion: When used in combination with HRA, this system could facilitate more selective biopsies and promote same-day AIN2+ treatment options by enabling real-time diagnosis., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are common among men who have sex with men (MSM). Many oropharyngeal and anorectal infections remain asymptomatic. We aimed to evaluate triple-site screening following PrEP introduction. We enrolled a prospective cohort study including 210 asymptomatic MSM during 2019-2020, analyzed by groups: HIV positive (HIV+), HIV-uninfected using PrEP (HIV-/PrEP+), or HIV-uninfected not using PrEP (HIV-/PrEP-). A self-administered questionnaire captured demographic information and sexual risk-taking behaviors. CT/NG testing results were compared between study groups and predictors of infection were evaluated. We included 59 HIV+, 70 HIV-/PrEP+, and 81 HIV-/PrEP- subjects. 30% ( n = 62) of participants tested positive for CT/NG. HIV-/PrEP+ group had highest proportion of infections ( n = 33, 47%) followed by HIV-/PrEP- ( n = 16, 22%) and HIV+ ( n =13, 20%; p < .001). Importantly, 98% (80/82) of pharyngeal/anorectal CT/NG infections were missed in genitourinary tract screening alone. PrEP use and previous syphilis infection were the strongest risk factor for CT/NG. Extra-genital asymptomatic CT/NG infections were prevalent among MSM. These data highlight the importance of routine extra-genital CT/NG testing in asymptomatic sexually active MSM. The study describes the consequences for three-site testing lack of implementation in the PrEP era.

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: Data on tissue distribution of human papillomavirus types in anal high-grade squamous intraepithelial lesions are limited and the impact on treatment outcomes poorly understood., Objective: We aimed to investigate potential predictors of treatment failure after electrocautery ablation, including human papillomavirus type(s) isolated from index lesions., Design: This was a retrospective cohort study., Settings: The study was conducted at a tertiary academic referral center in New York City., Patients: Seventy-nine HIV-infected patients with a diagnosis of anal high-grade squamous intraepithelial lesions between January 2009 and December 2012 were included, and genomic DNA was extracted from biopsy tissue., Main Outcome Measures: The prevalence of human papillomavirus types in index lesions and surveillance biopsies after electrocautery ablation were analyzed to evaluate treatment response., Results: Of 79 anal high-grade squamous intraepithelial lesions, 71 (90%) tested positive for ≥1 human papillomavirus type; 8 (10%) had no human papillomavirus detected. The most common type was 16 (39%), followed by 33 (15%). Human papillomavirus type 18 was seen in 3%. Sixty-one patients (77%) underwent electrocautery ablation and had subsequent surveillance biopsies. Surveillance biopsies yielded benign findings or low-grade squamous intraepithelial lesions in 31 (51%) of 61 and recurrent high-grade squamous intraepithelial lesions in 30 (49%) of 61 patients (mean follow-up: 35 mo). Ablation response did not differ significantly based on baseline demographics, smoking history, history of anogenital warts, mean CD4 T-cell count, antiretroviral-therapy use, and HIV viral load (<50 copies/mL). The recurrence of high-grade lesions was not significantly associated with high-risk human papillomavirus types detected in index lesions., Limitations: Human papillomavirus genotyping in surveillance biopsies was not performed., Conclusions: Anal high-grade squamous intraepithelial lesions in HIV-infected patients contain a wide range of human papillomavirus types, and individual lesions commonly harbor multiple types concomitantly. Recurrence of anal high-grade squamous intraepithelial lesions after electrocautery ablation occurs frequently and is not affected by high-risk human papillomavirus types. See Video Abstract at http://links.lww.com/DCR/A833.

Mycoplasma genitalium (MG) infection is a sexually transmitted infection that causes up to 25% of nongonococcal urethritis (NGU). MG strains carrying genetic markers of antimicrobial resistance that may affect treatment outcomes are increasingly recognized as a public health concern. We present two cases of persistent MG NGU with strains carrying both macrolide and quinolone resistance-associated mutations that were eradicated successfully by an extended course of minocycline.

Background: Although the benefit of chemoradiation over radiation therapy alone has been shown in randomized trials for stage II to III squamous cell of the anus, this benefit is not clear for patients with stage I cancer. Nevertheless, most societal recommendations endorse chemoradiation for patients with stage I squamous cell carcinoma of the anus despite the lack of proven benefit and potential increase in toxicity., Objective: The purpose of this study was to determine whether outcomes are improved with the addition of chemotherapy versus radiation alone for stage I squamous cell carcinoma of the anus., Design: This was a cohort analysis using Surveillance, Epidemiology and End Results registry linked to Medicare from 1996 to 2011. Propensity-score methods were used to control for potential confounding., Settings: This was a population-based study., Patients: Medicare eligible patients (age >65 y or with an eligible disability) with stage I squamous cell carcinoma of the anus treated with either definitive radiation alone or chemoradiation were included., Interventions: Radiation or chemoradiation was the intervention., Main Outcome Measures: Overall survival, disease-free survival, cause-specific survival, colostomy-free survival, and acute or late toxicities were measured., Results: A total of 200 patients with squamous cell carcinoma of the anus were identified who received chemoradiation versus 99 treated with lone radiotherapy. Median age was 72 years and did not differ by treatment (p = 0.6). Patients receiving chemoradiation had improved unadjusted overall survival compared with lone radiotherapy, but after adjustment using propensity-score methods there was no difference in overall survival (HR = 0.7 (95% CI, 0.4-1.0)), cause-specific survival (HR = 0.7 (95% CI, 0.3-1.6)), colostomy-free survival (HR = 1.1 (95% CI, 0.5-2.5)), or disease-free survival (HR = 0.9 (95% CI, 0.6-1.4)). Chemoradiation was associated with an increased risk of select early and late toxicities., Limitations: This is a retrospective series from an anonymous database. The data might not be relevant for younger, healthier patients., Conclusions: Lone radiation may be associated with adequate oncologic outcomes when used to treat older and sicker patients with stage I anal cancer. Physicians should discuss the potential benefits and harms of adding chemotherapy for the treatment of these patients. See Video Abstract at http://links.lww.com/DCR/A628.

Although human immunodeficiency virus-infected men who have sex with men are at high risk for anal cancer, little is known about the prevalence of anal dysplasia in human immunodeficiency virus (HIV)-infected transgender women. Our study found that prevalence rates of abnormal anal cytology and histology in HIV-infected transgender women were similar to those in HIV-infected men who have sex with men.

Background: Human immunodeficiency virus (HIV)-infected women have a higher burden of anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) compared with HIV-uninfected women. Guidelines for AC screening in this population are heterogeneous. Here we report outcomes and risk factors for anal HSIL following implementation of universal AC screening offered to all HIV-infected women., Methods: Data from women who underwent AC screening with anal cytology from April 2009 to July 2014 were analyzed. Routine clinical data included anal and cervical cytology, demographic/behavioral data, and high-resolution anoscopy (HRA) results. We evaluated the association of cytology with HRA results, and predictors of HSIL pathology, and compared rates of HSIL pathology among women meeting screening guidelines to those who did not., Results: Seven hundred forty-five HIV-infected women were screened with anal cytology. Thirty-nine percent had abnormal anal cytology on initial screen and 15% on secondary screen; 208 women underwent HRA following abnormal anal cytology. HSIL was found in 26% and 18% of anal biopsies following initial and secondary screening, respectively. One woman had AC. Cigarette smoking more than doubled HSIL risk. Among women who underwent AC screening despite not meeting existing guideline criteria, 21% and 10%, respectively, were found to have HSIL on biopsy. Neither meeting criteria for screening nor history of receptive anal sex was significantly associated with HSIL., Conclusions: Anal HSIL is common in HIV-infected women. Substantial numbers of HSIL would have been missed by strictly adhering to existing AC screening guidelines. These results support routine screening of all HIV-infected women regardless of human papillomavirus history or sexual practices., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

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 <0.001). Of the 728 HIV-infected patients with abnormal anal cytology who underwent HRA, 71% were MSM, 23% women, and 6% heterosexual men. HSIL/cancer was found in 32% of MSM, 26% of women, and 23% of heterosexual men (P = 0.3). There were five cases of anal squamous cell carcinoma (0.7%), four in MSM and one in a heterosexual man. In a multivariable adjusted analysis, biopsy-proven HSIL/cancer was associated with RAI [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.3-3.7]. CD4 T-cell counts more than 500/μl conferred a lower risk of HSIL/cancer (OR 0.5; 95% CI 0.3-0.9)., Conclusion: Rates of anal HSIL histology are high in HIV-infected patients of all sexual risk groups with abnormal anal cytology. Consequently, all HIV-infected patients may warrant anal cancer screening.