Anal cancer screening results from 18-to-34-year-old men who have sex with men living with HIV.

Men who have sex with men living with HIV (MSM LWH) are at highest risk for human papillomavirus (HPV)-associated anal cancer. There is no consensus on the optimal screening initiation age. This study aimed to assess the prevalence and severity of anal HPV disease among MSM LWH under the age of 35, which is a currently proposed screening age threshold. Between 2014 and 2020, 1255 18-to-34-year-old MSM LWH underwent anal cytology screening. 916 were co-tested for high-risk HPV (HR-HPV). 467 underwent high-resolution anoscopy (HRA) and biopsy. Cancer registry data were queried. Predictors of abnormal cytology (ie, ≥ASCUS) and histological high-grade squamous intraepithelial lesions (HSIL) were evaluated using unadjusted logistic regression models. Median age was 28 years (range, 18-34). 19% received at least one dose of HPV vaccine. Abnormal cytology rate was 65%. HR-HPV and HPV16 prevalence were 87% and 30%. Biopsy results were benign (10%), LSIL (43%) and HSIL (47%). No cases of prevalent or incident anal cancers were detected. Findings were similar between age subgroups (18-24, 25-29 and 30-34) except for a higher prevalence of AIN 3 in the 30-34 group (19%). Abnormal cytology was significantly associated with HR-HPV infection. Histological HSIL was associated with HR-HPV infection and cytological LSIL or worse. The absence of anal cancer in a large cohort of MSM LWH under the age of 35, despite high prevalence of anal HR-HPV infection and precancer, supports an age-based anal cancer screening strategy for MSM LWH.

Primary Anal Cancer Screening Results From 381 Women With Human Immunodeficiency Virus.

BACKGROUND: Women with human immunodeficiency virus (WWH) have an elevated risk for human papillomavirus (HPV)-associated anal cancer. Primary anal cancer screening results from this population could inform practice guidelines. METHODS: In total, 381 WWH with anal cytology screening, high-risk HPV (hrHPV) testing and genital (cervical or vaginal) cotesting within 6 months were identified during 2012-2019. Those with anal cytology of atypical squamous cells of undetermined significance (ASCUS) or worse underwent high-resolution anoscopy and biopsy. Independent predictors of anal hrHPV, HPV16, and histological anal high-grade squamous intraepithelial lesions (aHSIL) were identified using adjusted logistic regression models. RESULTS: Prevalence of anal hrHPV, HPV16, and ASCUS or worse cytology was 61%, 13%, and 68%. Histological aHSIL was detected in 42% of WWH with ASCUS or worse anal cytology. Prevalence of genital hrHPV, HPV16, and ASCUS or worse cytology was 30%, 4%, and 28%. Genital hrHPV predicted anal hrHPV (odds ratio [OR], 5.05), while genital HPV16 predicted anal HPV16 (OR, 9.52). Genital hrHPV and anal HPV16 predicted histological aHSIL (ORs, 2.78 and 10.9). CONCLUSIONS: Anal HPV disease was highly prevalent in this primary screening cohort of WWH. While genital screening results predicted anal disease, rates of isolated anal HPV disease were substantial, supporting universal anal cancer screening for this population.

Comparing Anal Cancer Screening Algorithms Using Cytology and Human Papillomavirus DNA Testing in 3 High-Risk Populations.

BACKGROUND: Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. Herein, we compare anal cytology to hrHPV DNA testing and 2 novel cytology/hrHPV cotesting algorithms among 3 high-risk populations. METHODS: Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1837 participants (1504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women). Performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between 4 strategies with distinct HRA referral thresholds: cytology (atypical squamous cells of undetermined significance, ASCUS); hrHPV testing (any hrHPV positive); algorithm A (benign cytology/HPV16/18 positive or ASCUS/hrHPV positive); and algorithm B (benign or ASCUS/hrHPV positive). RESULTS: Histological HSIL/cancer was detected in 756 (41%) participants. Cytology had the lowest sensitivity (0.76-0.89) but highest specificity (0.33-0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies/subgroups (range, 0.16-0.36). CONCLUSIONS: Screening algorithms that incorporate cytology and hrHPV testing significantly increased sensitivity but decreased specificity to detect anal precancer/cancer among high-risk populations.

Clinical Outcomes and Immunologic Characteristics of Coronavirus Disease 2019 in People With Human Immunodeficiency Virus.

We performed a retrospective study of coronavirus disease 2019 (COVID-19) in people with human immunodeficiency virus (PWH). PWH with COVID-19 demonstrated severe lymphopenia and decreased CD4+ T cell counts. Levels of inflammatory markers, including C-reactive protein, fibrinogen, D-dimer, interleukin 6, interleukin 8, and tumor necrosis factor α were commonly elevated. In all, 19 of 72 hospitalized individuals (26.4%) died and 53 (73.6%) recovered. PWH who died had higher levels of inflammatory markers and more severe lymphopenia than those who recovered. These findings suggest that PWH remain at risk for severe manifestations of COVID-19 despite antiretroviral therapy and that those with increased markers of inflammation and immune dysregulation are at risk for worse outcomes.

Electrocautery ablation of anal high-grade squamous intraepithelial lesions: Effectiveness and key factors associated with outcomes.

BACKGROUND: Electrocautery ablation (EA) is a common treatment modality for patients with anal high-grade squamous intraepithelial lesions (HSILs), but to the authors' knowledge its effectiveness has been understudied. The objective of the current study was to determine ablation outcomes and to identify clinicopathological factors associated with postablation disease recurrence. METHODS: A total of 330 people living with HIV with de novo intra-anal HSIL who were treated with EA from 2009 to 2016 were studied retrospectively. Using long-term, surveillance high-resolution anoscopy biopsy data, treatment failures were classified as local recurrence (HSIL noted at the treated site at the time of surveillance) or overall recurrence (HSIL noted at treated or untreated sites). The associations between these outcomes and clinical factors were analyzed using Cox proportional hazards models. RESULTS: Approximately 88% of participants were men who have sex with men. The median age of study  participants was 45.5 years (range, 35-51 years) and approximately 49% had multiple index HSILs (range, 2-6 index HSILs). At a median of 12.2 months postablation (range, 6.3-20.9 months postablation), approximately 45% of participants had developed local recurrence whereas 60% had developed overall recurrence. Current cigarette smoking, HIV viremia (HIV-1 RNA ≥100 copies/mL), and multiple index HSILs were found to be predictive of local recurrence. Overall recurrence was more common in current smokers and those with multiple index lesions. In multivariable models that included human papillomavirus (HPV) genotypes, baseline and persistent infections with HPV-16 and/or HPV-18 were found to be significantly associated with both local and overall recurrence. CONCLUSIONS: EA is an effective treatment modality for anal HSIL in people living with HIV, but rates of disease recurrence are substantial. Multiple index HSILs, HIV viremia, current cigarette smoking, and both baseline and persistent infection with HPV-16 and/or HPV-18 appear to negatively impact treatment success. Ongoing surveillance is imperative to capture recurrence early and improve long-term treatment outcomes.

HIV-positive women with anal high-grade squamous intraepithelial lesions: a study of 153 cases with long-term anogenital surveillance.

Women living with HIV (WLHIV) are at increased risk for human papillomavirus (HPV)-associated anal cancer. Given the "field effect" of HPV pathogenesis, some recommend that anal cancer screening should be limited to WLHIV with prior genital disease. This study aimed to characterize the relationship between anal and genital disease in WLHIV in order to better inform anal cancer screening guidelines. We retrospectively studied 153 WLHIV with biopsy-proven anal high-grade squamous intraepithelial lesions (AHSIL) and long-term evaluable cervical/vaginal/vulvar histopathology. Based on the absence or presence of genital HSIL, subjects were categorized as having isolated AHSIL or multicentric HSIL. Demographics, HIV parameters and cervical/anal HPV status were recorded. Chi-square test was used for bivariate analyses. Of 153 WLHIV with AHSIL, 110 (72%) had isolated AHSIL, while 43 (28%) had multicentric HSIL (28 cervical, 16 vulvar, and 8 vaginal HSIL). The median genital surveillance was 8 years (range 1-27). Cervical HPV16/18 infection was associated with multicentric disease (P = 0.001). Overall, 53% of multicentric cases presented genital HSIL preceding AHSIL with median interval 13 years (range 2-23). Paired anal and cervical high-risk HPV results were available for 60 women within 12 months of AHSIL diagnosis: 30 (50%) had anal infection alone, while 30 (50%) had anal/cervical coinfection by 16/18 (15%), non-16/18 (13%), or different types (22%). In conclusion, WLHIV frequently develop AHSILs without pre-existing genital disease or after long latency following a genital HSIL diagnosis. Our findings support anal cancer screening for WLHIV irrespective of prior genital disease.

HIV-Infected Patients With Anal Cancer Precursors: Clinicopathological Characteristics and Human Papillomavirus Subtype Distribution.

BACKGROUND: People living with HIV have high rates of anal human papillomavirus infection and anal precancer/cancer. OBJECTIVE: This study aims to: 1) determine human papillomavirus subtype distribution among people living with HIV with anal high-grade squamous intraepithelial lesions; 2) compare the clinicopathological characteristics of patients with anal high-grade squamous intraepithelial lesions by human papillomavirus 16 status; and 3) investigate high-risk human papillomavirus negative anal high-grade squamous intraepithelial lesion cases. DESIGN: In this retrospective study, 700 people living with HIV who have biopsy-proven anal high-grade squamous intraepithelial lesions were reviewed for demographics, cytological diagnoses, and human papillomavirus testing results for human papillomavirus 16, 18, and 12 other high-risk types. For human papillomavirus-negative subjects, corresponding biopsies were genotyped by using real-time polymerase chain reaction. SETTINGS: This study was conducted in a large urban HIV clinic system and major referral center for anal cancer screening. PATIENTS: Median age was 46 years (range, 20-76). Ninety-one percent of the patients were men who have sex with men. MAIN OUTCOME MEASURES: The primary outcome measure was the association between demographic variables and human papillomavirus 16 status. RESULTS: Anal cytology was unsatisfactory (5%), benign (13%), atypical squamous cells of undetermined significance (35%), low-grade squamous intraepithelial lesion (36%), and high-grade squamous intraepithelial lesions (11%). Human papillomavirus cotesting results were negative (n = 38, 5%), human papillomavirus 16 (n = 303, 43%), human papillomavirus 18 (n = 78, 11%), or exclusively non-16/18 types (n = 281, 40%). Human papillomavirus 16 positivity was associated with ≥3 high-grade lesions and ≥ low-grade squamous intraepithelial lesion cytology (p < 0.001). Age, race/ethnicity, sex, smoking, CD4+ T-cell count, and HIV viral load did not differ by status of human papillomavirus 16 (p > 0.05). For human papillomavirus-negative cases, human papillomavirus genotyping of biopsies was positive for high-risk (n = 14, 36%) or possibly carcinogenic types (n = 12, 32%), or negative (n = 12, 32%). LIMITATIONS: This was a retrospective data analysis, and it pooled the results for 12 high-risk human papillomavirus types rather than individual types. CONCLUSIONS: Nearly all people living with HIV and anal high-grade squamous intraepithelial lesions test positive for high-risk human papillomavirus on anal swabs; negative results may be due to sampling error, L1-based polymerase chain reaction assay, or human papillomavirus types not captured by standard clinical assays. Patients who have human papillomavirus 16-positive anal high-grade squamous intraepithelial lesions are indistinguishable from others based on demographic and clinical characteristics, underscoring the potential role of human papillomavirus testing for anal cancer screening. See Video Abstract at http://links.lww.com/DCR/B208. PACIENTES PORTADORES DE VIH CON PRECURSORES DE CÁNCER DE ANO: CARACTERÍSTICAS CLINICOPATOLÓGICAS Y DISTRIBUCIÓN DEL SUBTIPO VPH: Los pacientes portadores de VIH tienen altas tasas de infección por VPH y alto riesgo de desarrolar lesiones precáncerosas / cáncerosas del ano.(1) Determinar la distribución del subtipo de VPH entre las personas portadoras de VIH con lesiones intraepiteliales escamosas anales de alto grado. (2) Comparar las características clinicopatológicas de pacientes con lesiones intraepiteliales escamosas anales de alto grado del subtipo VPH 16. (3) Investigar casos de lesiones intraepiteliales escamosas anales de alto grado negativas para el VPH de alto riesgo.Estudio retrospectivo sobre 700 personas portadoras de VIH con lesiones intraepiteliales escamosas anales de alto grado confirmadas por biopsia. Los datos fueron revisados para determinar información demográfica, diagnósticos citológicos y resultados de tipización en el VPH subtipos 16 y 18, y otros 12 tipos de alto riesgo. Para los individuos negativos al VPH, se analizó el genotipo en las biopsias correspondientes mediante test de PCR en tiempo real.Extenso sistema de clinicas urbanas tratando VIH y un importante centro de referencia para la detección del cáncer analla mediana de edad poblacional fue de 46 años (rango, 20-76). 91% eran hombres que tenían sexo con hombres.Asociación entre las variables demográficas y el estado del VPH subtipo16.la citología anal fue insatisfactoria (5%), benigna (13%), células escamosas atípicas de importancia indeterminada (35%), lesión intraepitelial escamosa de bajo grado (36%) y lesiones intraepiteliales escamosas de alto grado (11%). Los resultados de la prueba conjunta del VPH fueron negativos (n = 38, 5%), el virus del VPH subtipo 16 (n = 303, 43%), el VPH subtipo 18 (n = 78, 11%) o los subtipos exclusivamente no 16/18 (n = 281, 40%). La positividad del VPH subtipo 16 se encotraba asociado con ≥3 lesiones de alto grado y ≥ células escamosas atípicas en la prueba de citología de indeterminada importancia (p < 0.001). La edad, la raza / etnia, el sexo, el tabaquismo, el recuento de células T CD4 + y la carga viral del VIH no difirieron según el estado del VPH subtipo 16 (p > 0.05). Para los casos negativos al VPH, el genotipo del virus del papiloma humano de las biopsias fue positivo para los tipos de alto riesgo (n = 14, 36%) o posiblemente carcinogénicos (n = 12, 32%), o negativo (n = 12, 32%).Análisis de datos retrospectivos, con resultados agrupados para 12 tipos de VPH de alto riesgo en lugar de tipos individuales.Casi todas las personas portadoras de VIH con lesiones intraepiteliales escamosas anales de alto grado dan positivo para el VPH de alto riesgo al muestreo de hisopos anales; Los resultados negativos pueden deberse a un error en el muestreo y al análisis de PCR basado en L1 o subtipos de VPH no obtenidos en los ensayos clínicos estándar. Los pacientes con lesiones intraepiteliales escamosas anales de alto grado positivas para el VPH subtipo 16 no son identificables de los demás, en función de las características demográficas y clínicas, lo que minimiza el rol potencial de la prueba del VPH en la detección del cáncer anal. Consulte Video Resumen en http://links.lww.com/DCR/B208. (Traducción-Dr. Xavier Delgadillo).

Anal Cancer Precursor Lesions in HIV-Infected Persons: Tissue Human Papillomavirus Type Distribution and Impact on Treatment Response.

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.

Risk of Invasive Anal Cancer in HIV-Infected Patients With High-Grade Anal Dysplasia: A Population-Based Cohort Study.

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.

Human Papillomavirus Genotypes Predict Progression of Anal Low-Grade Squamous Intraepithelial Lesions.

Background: High-risk human papillomavirus (hrHPV)-induced anal low-grade squamous intraepithelial lesions (LSILs) have the potential to progress to high-grade squamous intraepithelial lesions (HSILs). We investigated whether anal hrHPV infections, particularly types 16 and 18, predict LSIL-to-HSIL progression. Methods: One hundred forty-six human immunodeficiency virus (HIV)-infected and 22 HIV-uninfected patients with anal LSILs underwent cytology, HPV genotyping (16, 18, and pooled 12 hrHPV types), and high-resolution anoscopy-guided biopsy at baseline and surveillance. The associations between the rate of LSIL-to-HSIL progression and HPV types as well as longitudinal HPV-16/18 status were assessed by fitting separate Cox regression models. Results: At baseline, 91% of patients harbored hrHPV: HPV-16/18 (44%) and non-16/18 (86%). Upon follow-up (median, 20 [range, 6-36] months), 41% developed HSIL (84% at the same anatomic location as the initial LSIL and 16% at a different location). Baseline HPV-16/18-positive patients had greater probability of progression than patients with non-16/18 types or negative (67%, 25%, and 7%, respectively; P < .001). Persistent HPV-16/18 conferred the highest probability of progression (70%), followed by intermittent HPV-16/18 positivity (52%). In unadjusted and adjusted analyses, baseline and persistent HPV-16/18 were significantly associated with LSIL-to-HSIL progression. Conclusions: Anal LSIL patients who are positive for hrHPV, especially HPV-16/18, have an increased risk of developing HSIL. Type-specific HPV testing could serve as a risk stratification tool, providing prognostic information.

Differences in the Immune Microenvironment of Anal Cancer Precursors by HIV Status and Association With Ablation Outcomes.

Background: Anal high-grade squamous intraepithelial lesions (HSILs) are the precursors to anal cancer and frequently persist or recur following electrocautery ablation (EA). Impaired mucosal immunity may facilitate anal carcinogenesis. We characterized the immune microenvironment of anal HSILs in correlation with human immunodeficiency virus (HIV) serostatus and ablation outcomes. Methods: Using immunohistochemistry, mucosa-infiltrating CD4+ and CD8+ lymphocytes were quantified in HSILs and benign mucosa from 70 HIV+ and 45 HIV- patients. Clinicopathological parameters were compared. Results: Anal HSILs harbored more T lymphocytes than benign mucosa regardless of HIV status (P ≤ .03). Total T lymphocyte count and CD8+ subset were significantly higher in HIV+ HSILs versus HIV- HSILs (median cell count, 71 vs 47; 47 vs 22/high power field [HPF]; P < .001), whereas the CD4+ subset was comparable between groups (median, 24 vs. 25; P = .40). Post EA, HSILs persisted in 41% of HIV+ and 19% of HIV- patients (P = .04). Unadjusted analysis showed trends toward EA failures associated with HIV seropositivity (incidence rate ratio [IRR], 2.0; 95% CI, .8-4.9) and increased CD8+ cells (IRR, 2.3; 95% CI, .9-5.3). Conclusions: Human immunodeficiency virus is associated with alterations of the immune microenvironment of anal HSILs manifested by increased local lymphocytic infiltrates, predominately CD8+. Human immunodeficiency virus seropositivity and excess mucosa-infiltrating CD8+ cells may be associated with ablation resistance.

A Population-Based Cohort Analysis of Chemoradiation Versus Radiation Alone for Definitive Treatment of Stage I Anal Cancer in Older Patients.

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.

High Rates of Anal High-Grade Squamous Intraepithelial Lesions in HIV-Infected Women Who Do Not Meet Screening Guidelines.

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.

Shedding of Hepatitis C Virus Into the Rectum of HIV-infected Men Who Have Sex With Men.

BACKGROUND: For over a decade we have known of an epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM), but there still remains significant controversy over which bodily fluid(s) are responsible for HCV transmission in these men. METHODS: We enrolled HIV-infected MSM with recent and chronic HCV infection and quantified HCV from rectal fluid obtained by blind swab. We compared the rectal HCV viral load (VL) with paired blood HCV VL. RESULTS: We found rectal HCV shedding in 20 (47%) of 43 men, only one (2%) of whom had visible bleeding. Detection of rectal HCV shedding was associated with blood VL > 5 log10 IU/mL (p = .01), and 85% with blood VL > 5 log10 IU/mL had rectal shedding. The HCV VL of the rectal fluid ranged from 2.6 to 5.5 log10 IU/mL. Based on the median rectal fluid VL, the surface of an average human penis would be exposed to at least 2,300 IU of HCV for the duration of anal intercourse. CONCLUSION: This study provides the first direct evidence to our knowledge that a sufficient quantity of HCV is shed into the rectum in HIV-infected men with HCV infection to directly infect an inserted penis or be passed indirectly through fomite-like transmission to the rectum of sex partner. We must develop an appropriate public health campaign to educate MSM about these routes of HCV infection to reverse the HCV epidemic among HIV-infected MSM.

Prevalence of Anal Dysplasia in Human Immunodeficiency Virus-Infected Transgender Women.

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.

Host Nuclear Genome Copy Number Variations Identify High-Risk Anal Precancers in People Living With HIV.

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.

Automated In Vivo High-Resolution Imaging to Detect Human Papillomavirus-Associated Anal Precancer in Persons Living With HIV.

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.

Deployment and assessment of a deep learning model for real-time detection of anal precancer with high frame rate high-resolution microendoscopy.

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.

Gay and Bisexual Men Who Report Anal Sex Stigma Alongside Discomfort Discussing Anal Sex with Health Workers Are Less Likely to Have Ever Received an Anal Examination or Anal Swab.

Purpose: We sought to determine whether stigma toward anal sexuality was associated with having ever received an anal examination or anal swab among gay and bisexual men (GBM). Methods: In 2017, we conducted a cross-sectional online survey with 1513 adult cisgender GBM living in the United States. We used structural equation modeling to test whether the Anal Sex Stigma Scales (a validated measure comprising provider stigma, self-stigma, and silence) was negatively associated with lifetime receipt of anorectal examination or anal swabbing by a medical provider. The model assessed mediation by respondents' comfort discussing anal sex practices with health workers and adjusted for possible confounders. Results: As hypothesized, anal sex stigma was associated with less comfort discussing anal sex (ß = -0.44, 95% confidence interval [CI]: -0.50 to -0.38, p < 0.001), and greater comfort was associated with greater likelihood of screening (ß = 0.28, 95% CI: 0.19 to 0.37, p < 0.001). The model demonstrated good fit (root mean square error of approximation = 0.045, comparative fit index, and Tucker-Lewis index each = 0.99) and adjusted for everyday discrimination, social support specific to anal sex, age, income, education, medical coverage, outness, and ethnic/racial identification. Collectively, model variables accounted for 48% of the variance in screening (p < 0.001). Conclusion: GBM who endorsed less anal sex stigma reported greater comfort discussing anal sex with health workers and were more likely to have ever received anal health screening by a medical provider. To improve anal health and cancer prevention among GBM, anal sex stigma and related discomfort discussing anal sex with health workers are targets for intervention.