Search

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.

Anal human papillomavirus (HPV) disproportionately affects men who have sex with men (MSM), particularly those who are older and those living with HIV. After experiencing difficulty recruiting older MSM into a study on aging and anal HPV, we conducted a sub-study to gain feedback on our recruitment methods and explore barriers and facilitators to participating in anal HPV research. We conducted focus groups with 30 men who have sex with men (MSM), both HIV-negative and MSM living with HIV, ages 50-75. We identified multiple themes that were barriers to participation including: (1) lack of knowledge about human papillomavirus and anal cancer; (2) research focused on anal cancer or discomfort with topics or procedures concerning the anus; (3) stigma including stigma associated with being men who have sex with men, being out, being a receptive partner, and being considered "older" in the gay community; and (4) confidentiality concerns including a fear of breach of confidentiality. Facilitators to participation were also identified; these motivational factors include altruism, wanting recommendations from a doctor, and desire to receive the best available care. Researchers seeking to enroll older men who have sex with men should be aware of these barriers and facilitators to participation in order to maximize recruitment.

BackgroundMen who have sex with men (MSM) living with human immunodeficiency virus (HIV) are at increased risk of anal cancer. Anal cytology can be used to screen for dysplasia, with high-resolution anoscopy (HRA) required for diagnostic confirmation. We describe the impact lack of HRA had on management of abnormal screening results in Bogotá, Colombia.Material and methodsThis retrospective cohort study includes MSM with HIV who underwent anal cytology screening between January 2019February 2020, with colorectal surgery (CRS) follow-up through July 2020. Cytology results included atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). Categorical and continuous variables were compared via Fisher's exact test and Wilcoxon rank-sum, respectively.ResultsOf 211 MSM screened, 68 had abnormal cytology: ASC-US (n = 23), LSIL (n = 41), HSIL (n = 4). Sixty (88.2%) were referred to CRS, and 51 (75.0%) attended ≥ 1 appointment. At initial assessment, 17 were referred for anal exam under anesthesia (EUA) for tissue resection, and 21 for rectosigmoidoscopy. Having perianal condyloma was associated with recommendation for EUA (P < 0.001), while cytology grade of dysplasia was not (P = 0.308). Eleven (16.2%) underwent EUA for condyloma resection.ConclusionsFew studies have described anal cancer screening in settings without HRA. We found lack of HRA limited management of abnormal cytology in Colombia. Those with condyloma underwent resection, but HRA remains necessary to localize and treat microscopic disease. Next steps include implementation of HRA in order to further develop the anal cancer screening program for MSM with HIV in Bogotá.

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.

Anal adenocarcinoma combined with perianal Paget’s disease (PPD) involving the vulva is rare, and there is no established standard treatment. We present the case of a 69-year-old woman with symptoms of intermittent hematochezia and perianal discomfort for 7 months. Upon examination, we discovered a plaque-like hard mass on the right posterior wall of the anal canal, which extended to encompass the anus and dentate line. The lesion skin also extended forward from the gluteal groove, involving the bilateral labial area. Colonoscopy revealed an extensive protruding lesion on the dentate line, which was confirmed as anal adenocarcinoma (mrT4N0M0). The presence of Paget’s cells in perianal and vulvar skins led to the diagnosis of PPD. The strategy of neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery was then made after multi-disciplinary discuss. The scope and extent of perianal and vulvar disease were significantly diminished after nCRT. The patient underwent laparoscopic abdominoperineal resection and vulvar lesion resection, confirming the diagnosis of anal adenocarcinoma (ypT2N0). No evidence of tumor cells was found in perianal and vulvar skin, indicating a complete response. The patient is regularly monitored without recurrence or metastasis.

Objectives: A published tumour regression grade (TRG) score for squamous anal carcinoma treated with definitive chemoradiotherapy based on T2-weighted MRI yields a high proportion of indeterminate responses (TRG-3). We investigate whether the addition of diffusion-weighted imaging (DWI) improves tumour response assessment in the early post treatment period. Materials and methods: This retrospective observational study included squamous anal carcinoma patients undergoing MRI before and within 3 months of completing chemoradiotherapy from 2009 to 2020. Four independent radiologists (1–20 years' experience) scored MRI studies using a 5-point TRG system (1 = complete response; 5 = no response) based on T2-weighted sequences alone, and then after a 12-week washout period, using a 5-point DWI-TRG system based on T2-weighted and DWI. Scoring confidence was recorded on a 5-point scale (1 = low; 5 = high) for each reading and compared using the Wilcoxon test. Indeterminate scores (TRG-3) from each reading session were compared using the McNemar test. Interobserver agreement was assessed using kappa statistics. Results: Eighty-five patients were included (mean age, 59 years ± 12 [SD]; 55 women). T2-weighted TRG-3 scores from all readers combined halved from 24% (82/340) to 12% (41/340) with DWI (p < 0.001). TRG-3 scores changed most frequently (41%, 34/82) to DWI-TRG-2 (excellent response). Complete tumour response was recorded clinically in 77/85 patients (91%). Scoring confidence increased using DWI (p < 0.001), with scores of 4 or 5 in 84% (287/340). Interobserver agreement remained fair to moderate (kappa range, 0.28–0.58). Conclusion: DWI complements T2-weighted MRI by reducing the number of indeterminate tumour responses (TRG-3). DWI increases radiologist's scoring confidence. Clinical relevance statement: Diffusion-weighted imaging improves T2-weighted tumour response assessment in squamous anal cancer, halving the number of indeterminate responses in the early post treatment period, and increases radiologists' confidence. Key Points: Tumour response based on T2-weighted MRI is often indeterminate in squamous anal carcinoma. Diffusion-weighted imaging alongside T2-weighted MRI halved indeterminate tumour regression grade scores assigned by four radiologists from 24 to 12%. Scoring confidence of expert and non-expert radiologists increased with the inclusion of diffusion-weighted imaging. [ABSTRACT FROM AUTHOR]

ObjectivesThe Lower Anogenital Squamous Terminology (LAST) recommendations classify human papillomavirus-associated squamous lesions into low- and high-grade squamous intraepithelial lesions (LSILs/HSILs). Our study aimed to assess interobserver agreement among 6 experienced pathologists in assigning 40 anal lesions previously diagnosed as anal intraepithelial neoplasia 2 (AIN 2) to either HSIL or non-HSIL categories.MethodsAgreement based on photomicrographs of H&E alone or H&E plus p16 immunohistochemistry was calculated using κ coefficients.ResultsAgreement was fair based on H&E alone (κ = 0.42; 95% confidence interval [CI], 0.34-0.52). Adding p16 improved agreement to moderate (κ = 0.55; 95% CI, 0.54-0.62). On final diagnosis, 21 cases (53%) had unanimous diagnoses, and 19 (47%) were divided. When designating p16 results as positive or negative, agreement was excellent (κ = 0.92; 95% CI, 0.83-0.95). Among variables (staining location, extent, and intensity), staining of the basal/parabasal layers was a consistent feature in cases with consensus for positive results (20/20). Of the 67 H&E diagnoses with conflicting p16 results, participants modified 32 (48%), downgrading 23 HSILs and upgrading 9 non-HSILs.ConclusionsAlthough p16 increased interobserver agreement, disagreement remained considerable regarding intermediate lesions. p16 expression, particularly if negative, can reduce unwarranted HSIL diagnoses and unnecessary treatment.

Patients with systemic lupus erythematosus have a higher incidence of neoplasms associated with human papillomavirus infections, such as those that affect the vulva, the vagina, and the cervix; however, little is known about the frequency of anal cancer among these patients. Although there are recommendations for screening for this cancer in immunosuppressed individuals, it is possible that this procedure is not strictly followed. We describe the case of a 47-year-old woman with systemic lupus erythematosus who was treated with immunosuppressants and developed advanced anal squamous cell carcinoma after adequate treatment and healing of a high-grade cervical squamous intraepithelial lesion. Five years after the completion of the anal cancer treatment, the patient presented with cystic hepatic lesions that were histopathologically confirmed to be metastatic squamous cell carcinoma. This report aimed to highlight the need for anal cancer screening in patients with lupus, particularly if there was a history of cervical cytopathological alterations.

Gay, bisexual, and other men who have sex with men (MSM) experience disproportionately high burdens of Human Papilloma Virus (HPV)-associated anal cancers. Recent focus has shifted to anorectal cancer prevention through high-resolution anoscopy (HRA); however, little is known about sexual minority men's perceptions, attitudes, or beliefs regarding HRA. We conducted 4 qualitative Focus Group Discussions (FGDs) (n = 15) with sexual minority men, focusing on their beliefs, attitudes, and perceptions of undergoing HRA. Participants discussed their experiences of HPV/HRA as influenced by both their gender and sexuality, including unawareness of HPV disease as a male health issue, challenges relating to female-oriented HPV/HRA language, conception of HPV/HRA as related to prostate health, and connecting their sexual behavior identification as "bottoms" to their need for HRA. As efforts to improve HRA knowledge, access, and uptake among sexual and gender minority communities increase, special attention should be paid to language and messaging choices around HRA.

ObjectiveAnal cancer is an uncommon malignancy with the primary treatment for localized disease being concurrent radiation and chemotherapy. Pre-treatment PET/CT is useful for target delineation, with minimal exploration of its use in prognostication. In the post-treatment setting there is growing evidence for advanced PET metrics in assessment of treatment response, and early identification of recurrence essential for successful salvage, however this data is limited to small series.MethodsPatient with non-metastatic anal cancer from a single institution were retrospectively reviewed for receipt of pre- and post-treatment PET/CTs. PET data was co-registered with radiation therapy planning CT scans for precise longitudinal assessment of advanced PET metrics including SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), for assessment with treatment outcomes. Treatment outcomes included local recurrence (LR), progression free survival (PFS), and overall survival (OS), as defined from the completed radiation therapy to the time of the event. Cox proportional hazard modeling with inverse probability weighting (IPW) using the propensity score based on age, BMI, T-stage, and radiation therapy dose were utilized for assessment of these metrics.ResultsFrom 2008 to 2017 there were 72 patients who had pre-treatment PET/CT, 61 (85%) had a single follow up PET/CT, and 35 (49%) had two follow up PET/CTs. The median clinical follow-up time was 25 months (IQR: 13-52) with a median imaging follow up time of 16 months (IQR: 7-29). On pre-treatment PET/CT higher MTV2.5 and TLG were significantly associated with higher risk of local recurrence (HR 1.11, 95% CI: 1.06-1.16, p

Background & aimWomen with HIV/HPV coinfection and cervical lesions are at increased risk of developing HPV related anal cancer. Self-collection of anal swabs may facilitate HPV molecular testing in anal cancer screening, especially in high-risk groups, and yet it is not adequately studied. We evaluated level of agreement between self-collected anal swabs (SCAS) and clinician-collected anal swabs (CCAS) when used for HPV genotyping. We also described the anal HPV genotype distribution and HIV/HPV coinfection.MethodsWe performed a cross sectional study with participants from a visual-inspection-with-acetic-acid and cervicography (VIAC) clinic, in Harare, Zimbabwe. In a clinic setting, the women aged ≥18 years provided anal swabs in duplicate; first CCAS and then SCAS immediately after. HPV detection and genotyping were performed using next generation amplicon sequencing of a 450bp region of the HPV L1 gene. Level of agreement of HPV genotypes between CCAS and SCAS was calculated using the kappa statistic. McNemar tests were used to evaluate agreement in the proportion of genotypes detected by either method.ResultsThree-hundred women provided 600 samples for HPV genotyping. HPV genotypes were detected in 25% of SCAS and in 22% of CCAS. The most common genotypes with CCAS were HPV52, HPV62 and HPV70 and with SCAS were HPV62, HPV44, HPV52, HPV53 and HPV68. Total HPV genotypes detected in CCAS were more than those detected in SCAS, 32 versus 27. The agreement of HPV genotypes between the two methods was 0.55 in kappa value (k). The test of proportions using McNemar gave a Chi-square value of 0.75 (p = 0.39). Multiple HPV infections were detected in 28/75 and 29/67 women for CCAS and SCAS respectively.ConclusionsSCAS and CCAS anal swabs showed moderate agreement, with no statistically significant difference in the proportion of genotypes detected by either methods. Although the differences between the two methods were not statistically significant, CCAS detected more HPV genotypes than SCAS and more HPV infections were detected in SCAS than in CCAS. Our data suggest that self-collected anal swabs can be used as an alternative to clinician-collected anal swabs for HPV genotyping.

BACKGROUND: Anal precancers and cancers can be detected during screening with high-resolution anoscopy (HRA). The sensitivity of HRA depends on the burden and duration of human papillomavirus (HPV) among those screened as well as anoscopist proficiency, which is highly correlated with prior screening experience. Our objective was to compare the identification and type of HPV and the likelihood of HRA-detected precancer for men who have sex with men (MSM) undergoing their first HRA-screening in Nigeria. METHODS: MSM were recruited from an HIV test-and-treat cohort, TRUST/RV368, into a new anal cancer screening program. Anal swabs obtained during screening underwent Ion Torrent next-generation sequencing using barcoded HPV PCR broad-spectrum primers 5+/6+ to detect up to 161 HPVs. All high-risk (HR) HPVs and the most abundant low-risk (LR)-HPVs were evaluated as type-specific infections with some categorized as belonging to a multiple infection. HRA screening results included benign, low-grade squamous intraepithelial lesions (LSIL), or HSIL as detected by cytology or histology. Multivariable logistic regression was used to assess the association of HPV and other cofactors with any SIL. RESULTS: Among 342 MSM, 60% were HIV-infected, 89% were under 35 years of age, and 51% had 8 or more years since anal coital debut. Of those with SIL, 89% had LSIL and only 11% had HSIL. Prevalence of any HPV and high-risk (HR)-HPV was 92% and 74%, respectively. The most prevalent genotypes in rank order were HPV6 (31%), HPV16 (23%), HPV42 (20%), HPV11 (18%), HPV45 (18%), and HPV51 (17%). For multiple HR-HPVs, 31% had a single HR-HPV, 32% had 2-3, and 10% had 4 or more. Low-risk HPVs, type 6 and/or 11, were common (42%) and were significantly associated with SIL (adjusted odds ratio [aOR]:1.8, 95% confidence interval [CI]: 1.1-3.1) together with perianal warts (aOR:6.7, 95% CI: 3.3-13.5). In contrast, HR-HPV and multiple HR-HPVs were not significantly associated with SIL (all p > 0.05). CONCLUSIONS: Detection of HSIL was low. Although HR-HPV was abundant, HSIL development also depends on the duration of HR-HPV infections and the anoscopists level of experience. As our cohort ages and the anoscopist becomes more skilled, detection of HSIL will likely improve.

ObjectiveHIV-infected women (WLHIV) have more than 10-fold higher risk for squamous cell cancer of the anus. Experts suggest cytology-based strategies developed for cervical cancer screening may prevent anal cancer by detecting anal cytologic or histological high-grade squamous intraepithelial lesion (hHSIL) for treatment. Currently, there is no consensus on anal-hHSIL screening strategies for WLHIV.DesignBetween 2014 and 2016, 276 WLHIV were recruited at 12 US AIDS Malignancy Consortium clinical trials sites to evaluate hHSIL prevalence and (test) screening strategies.MethodsParticipants completed detailed questionnaire, underwent anal assessments including high-risk human papillomavirus (hrHPV) testing using hrHPV-Hybrid Capture 2 (HC2) and hrHPV-APTIMA, anal cytology, and concurrent high-resolution anoscopy. Screening test characteristics for predicting hHSIL validated by central review of histologic diagnosis were estimated sensitivity, specificity, positive predictive value, and false-omission rate. Paired analyses compared sensitivity and specificity for hrHPV single tests to anal cytology alone.Results83% (229/276) of enrolled WLHIV had complete anal assessment data and were included in this analysis. Mean age was 50, 62% black and 60 (26%) had hHSIL. Anal cyotology (>atypical squamous cells of undetermined significance), hrHPV-HC2, and hrHPV-APTIMA sensitivity estimates were similarly high (83, 77, and 75%, respectively, P values > 0.2). Specificity was higher for both hrHPV-APTIMA and hrHPV-HC2 compared with anal cytology (67 vs. 50%, P atypical squamous cells of undetermined significance) to predict anal hHSIL. Among tests with similar sensitivity, the specificity was significantly higher for hrHPV-APTIMA and hrHPV-HC2. Thus, anal hrHPV testing may be an important alternative strategy to anal cytology for anal hHSIL screening among WLHIV.

BACKGROUND:Men who have sex with men (MSM) living with HIV are at increased risk for anal cancer. We evaluated satisfaction with first-time anal cancer screening using high resolution anoscopy (HRA) as a cross sectional survey among men who have sex with men (MSM) attending a community-engaged clinic in Abuja, Nigeria. METHODS:Between March and August 2017, 342 MSM underwent screening and 307 (89%) completed a satisfaction survey that evaluated 8 domains related to expectations, convenience, staff interpersonal skills, physical surroundings, technical competence, pain/discomfort, general satisfaction, and intention to re-screen if symptomatic. The 22-item questionnaire used 5-point Likert scales ranging from 1 (strongly disagree) to 5 (strongly agree). For each domain, responses to specific items were averaged, aggregated, and converted to a 100-point scaled score (SS) with 25 and 75 corresponding to disagree and agree, respectively. RESULTS:Median age was 24 years (interquartile range [IQR]: 22-28), median years since anal coital debut was 7 (IQR: 4-12), and 58% (95% confidence interval [CI]: 52-64%) were living with HIV. Despite respondents reporting pre-procedure anxiety (SS:73), most were comfortable with the setting and procedure and reported overall satisfaction (SS:74-76). Willingness to undergo future screening had the lowest score (SS:69) within the general satisfaction domain. The lowest scoring domains were pain/discomfort (SS:57) and agreement to re-screen if symptomatic (SS:59), which correlated with lower overall satisfaction (p  0.006) or number of anal biopsies (all p > 0.05). CONCLUSIONS:Overall, HRA was satisfactory for those naïve to screening but moving forward necessitates monitoring levels of discomfort with pain scales and normalizing dialogue around clinical symptoms of anal cancer and overall anal health to sustain future screening.

BackgroundAnal precancers and cancers can be detected during screening with high-resolution anoscopy (HRA). The sensitivity of HRA depends on the burden and duration of human papillomavirus (HPV) among those screened as well as anoscopist proficiency, which is highly correlated with prior screening experience. Our objective was to compare the identification and type of HPV and the likelihood of HRA-detected precancer for men who have sex with men (MSM) undergoing their first HRA-screening in Nigeria.MethodsMSM were recruited from an HIV test-and-treat cohort, TRUST/RV368, into a new anal cancer screening program. Anal swabs obtained during screening underwent Ion Torrent next-generation sequencing using barcoded HPV PCR broad-spectrum primers 5+/6+ to detect up to 161 HPVs. All high-risk (HR) HPVs and the most abundant low-risk (LR)-HPVs were evaluated as type-specific infections with some categorized as belonging to a multiple infection. HRA screening results included benign, low-grade squamous intraepithelial lesions (LSIL), or HSIL as detected by cytology or histology. Multivariable logistic regression was used to assess the association of HPV and other cofactors with any SIL.ResultsAmong 342 MSM, 60% were HIV-infected, 89% were under 35 years of age, and 51% had 8 or more years since anal coital debut. Of those with SIL, 89% had LSIL and only 11% had HSIL. Prevalence of any HPV and high-risk (HR)-HPV was 92% and 74%, respectively. The most prevalent genotypes in rank order were HPV6 (31%), HPV16 (23%), HPV42 (20%), HPV11 (18%), HPV45 (18%), and HPV51 (17%). For multiple HR-HPVs, 31% had a single HR-HPV, 32% had 2-3, and 10% had 4 or more. Low-risk HPVs, type 6 and/or 11, were common (42%) and were significantly associated with SIL (adjusted odds ratio [aOR]:1.8, 95% confidence interval [CI]: 1.1-3.1) together with perianal warts (aOR:6.7, 95% CI: 3.3-13.5). In contrast, HR-HPV and multiple HR-HPVs were not significantly associated with SIL (all p > 0.05).ConclusionsDetection of HSIL was low. Although HR-HPV was abundant, HSIL development also depends on the duration of HR-HPV infections and the anoscopist's level of experience. As our cohort ages and the anoscopist becomes more skilled, detection of HSIL will likely improve.

Objective This study aims to report the case of a 69-year-old female patient with a diagnosis of anorectal melanoma (AM) established by immunohistochemistry.

Purpose: To determine whether treatment of anal high-grade squamous intraepithelial lesions (HSIL), vs active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV, the US National Cancer Institute funded the Phase III ANal Cancer/HSIL Outcomes Research (ANCHOR) clinical trial. As no established patient-reported outcomes (PRO) tool exists for persons with anal HSIL, we sought to estimate the construct validity and responsiveness of the ANCHOR Health-Related Symptom Index (A-HRSI). Methods: The construct validity phase enrolled ANCHOR participants who were within two weeks of randomization to complete A-HRSI and legacy PRO questionnaires at a single time point. The responsiveness phase enrolled a separate cohort of ANCHOR participants who were not yet randomized to complete A-HRSI at three time points: prior to randomization (T1), 14–70 (T2), and 71–112 (T3) days following randomization. Results: Confirmatory factor analysis techniques established a three-factor model (i.e., physical symptoms, impact on physical functioning, impact on psychological functioning), with moderate evidence of convergent validity and strong evidence of discriminant validity in the construct validity phase (n = 303). We observed a significant moderate effect for changes in A-HRSI impact on physical functioning (standardized response mean = 0.52) and psychological symptoms (standardized response mean = 0.60) from T2 (n = 86) to T3 (n = 92), providing evidence of responsiveness. Conclusion: A-HRSI is a brief PRO index that captures health-related symptoms and impacts related to anal HSIL. This instrument may have broad applicability in other contexts assessing individuals with anal HSIL, which may ultimately help improve clinical care and assist providers and patients with medical decision-making. [ABSTRACT FROM AUTHOR]

BackgroundAnal squamous cell carcinoma (ASCC) is uncommon, yet seen more frequently in the setting of the human immunodeficiency virus (HIV). Chemoradiotherapy is the definitive modality of treatment for patients with ASCC; this study examines factors impacting clinical outcomes in a large cohort of HIV-positive and HIV-negative patients.MethodsA retrospective review was conducted of patients treated for nonmetastatic ASCC at a single institution between 2005 and 2018. Freedom from local recurrence (FFLR), freedom from distant metastasis, and overall survival (OS) were calculated using the Kaplan-Meier method, and univariate and multivariate analysis were performed using the Cox proportional hazards model.ResultsDuring the study period, 111 patients initiated definitive treatment for ASCC. Median age of the entire cohort was 56.7 years (interquartile range, 51.5-63.5), with 52 patients (46.8%) being HIV-positive. At median follow-up of 28.0 months, the 2- and 5-year FFLR were 78.2% (95% confidence interval [CI], 70.4-87.0) and 74.6% (95% CI, 65.8-84.5), respectively. Multivariate analysis revealed time from diagnosis to treatment initiation (median, 8 weeks; hazard ratio, 1.06; 95% CI, 1.03-1.10) to be significantly associated with worse FFLR and OS. HIV-positive patients had a trend toward worse FFLR (log-ranked p = .06). For HIV-positive patients with post-treatment CD4 less than 150 cells per mm3 , there was significantly worse OS (log-ranked p = .015).ConclusionA trend toward worse FFLR was seen in HIV-positive patients, despite similar baseline disease characteristics as HIV-negative patients. Worse FFLR and OS was significantly associated with increased time from diagnosis to treatment initiation. Poorer OS was seen in HIV-positive patients with a post-treatment CD4 count less than 150 cells per mm3 .Implications for practiceHuman immunodeficiency virus (HIV)-positive patients with anal squamous cell carcinoma can represent a difficult clinical scenario. Definitive radiation with concurrent chemotherapy is highly effective but can result in significant toxicity and a decrease in CD4 count that could predispose to HIV-related complications. As HIV-positive patients have largely been excluded from prospective clinical trials, this study seeks to provide greater understanding of their outcomes with radiation therapy, potential predictors of worse local control and overall survival, and those most at risk after completion of treatment.

BackgroundSquamous cell carcinoma of the anus (SCCA) incidence is rising in the United States. Study of incidence trends by stage at diagnosis, age-specific and birth cohort patterns, and trends in mortality could provide evidence for a true increase and etiological clues for the increase in incidence.MethodsUsing the US Cancer Statistics dataset, we examined trends in SCCA incidence (2001-2015) and mortality (2001-2016) rates. Join-point regression was used to compute annual and average annual percentage change (AAPC). Incidence patterns by 5-year age group and birth cohort were evaluated using incidence rate ratios (IRRs) and age-period-cohort modeling.ResultsSCCA incidence increased 2.7% per year (95% confidence interval [CI] = 2.1% to 3.3%), with pronounced increases in age groups 50 years and older. Distant-stage SCCA incidence tripled (AAPC = 8.6%, 95% CI = 5.4% to 12.0%, among men and AAPC = 7.5%, 95% CI = 4.8% to 10.2%, among women) and regional-stage SCCA incidence nearly doubled (AAPC = 4.7% for men and women) in both sexes; the AAPC for localized stage was 1.3% (95% CI = 0.6% to 2.0%) in men and 2.3% (95% CI = 1.8% to 2.8%) in women. Compared with adults born circa 1946, recently born black men (born circa 1986) had a nearly fivefold higher risk (IRR = 4.7, 95% CI = 2.1 to 10.2) of SCCA, and the risk doubled among white men (IRR = 2.0, 95% CI = 1.7 to 2.2) and white women (IRR = 2.1, 95% CI = 1.9 to 2.3) born after circa 1960. Anal cancer mortality rates increased 3.1% per year (95% CI = 2.6% to 3.5%) with statistically significant increases in age groups 50 years and older. SCCA incidence-based mortality increased 1.9% annually (95% CI = 0.5% to 3.4%), with a notable (4.9%, 95% CI = 2.4% to 7.3%, per year) rise in adults ages 60-69 years.ConclusionThe increase in SCCA incidence, particularly advanced-stage disease, and a similar increase in mortality suggest a true increase in the occurrence of SCCA. Future research and improved prevention are urgently needed to mitigate the increasing disease burden.

BACKGROUND: Women 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. METHODS: The 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. RESULTS: We 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]). CONCLUSIONS: The prevalence of anal hHSIL in WLHIV in the United States was 27% in this study where all participants received high-resolution anoscopy and biopsy.

BackgroundPeople living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk.MethodsWe studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion.ResultsCumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for

BACKGROUND: Socioeconomic status (SES) is associated with diagnostic and treatment delays and survival in multiple cancers, but less data exist for anal squamous cell carcinoma (ASCC). This study investigated the association between SES and outcomes for patients undergoing definitive chemoradiation therapy for ASCC. METHODS: One hundred and eleven patients diagnosed with nonmetastatic ASCC between 2005 and 2018 were retrospectively reviewed. Socioeconomic predictor variables included primary payer, race, income, employment, and partnership status. Outcomes included the tumor-node (TN) stage at diagnosis, the duration from diagnosis to treatment initiation, relapse-free survival (RFS), and overall survival (OS). Age, gender, TN stage, and HIV status were analyzed as covariates in survival analysis. RESULTS: SES was not associated with the TN stage at diagnosis. SES factors associated with treatment initiation delays were Medicaid payer (P = .016) and single partnership status (P = .016). Compared to privately insured patients, Medicaid patients had lower 2-year RFS (64.4% vs 93.8%, P = .021) and OS (82.9% vs 93.5%, P = .038). Similarly, relative to patients in the racial majority, racial minority patients had lower 2-year RFS (53.3% vs 93.5%, P = .001) and OS (73.7% vs 92.6%, P = .008). Race was an independent predictor for both RFS (P = .027) and OS (P = .047). CONCLUSIONS: These results highlight the impact of social contextual factors on health. Interventions targeted at socioeconomically vulnerable populations are needed to reduce disparities in ASCC outcomes.

PurposeAnal cancer risk is substantially higher among HIV-infected men who have sex with men (MSM) as compared with other reproductive-age adults, but screening is rare across sub-Saharan Africa. We report the use of high-resolution anoscopy (HRA) as a first-line screening tool and the resulting early outcomes among MSM in Abuja, Nigeria.MethodsFrom August 2016 to August 2017, 424 MSM enrolled in an anal cancer screening substudy of TRUST/RV368, a combined HIV prevention and treatment cohort. HRA-directed biopsies were diagnosed by histology, and ablative treatment was offered for high-grade squamous intraepithelial lesions (HSIL). HRA proficiency was assessed by evaluating the detection of squamous intraepithelial lesions (SIL) over time and the proportion biopsied. Prevalence estimates of low-grade squamous intraepithelial lesions and HSIL with 95% CIs were calculated. Multinomial logistic regression was used to identify those at the highest risk of SIL.ResultsMedian age was 25 years (interquartile range [IQR], 22-29), median time since sexual debut was 8 years (IQR, 4-12), and 59% (95% CI, 54.2% to 63.6%) were HIV infected. Rate of detection of any SIL stabilized after 200 screenings, and less than 20% had two or more biopsies. Preliminary prevalence estimates of low-grade squamous intraepithelial lesions and HSIL were 50.0% (95% CI, 44.7% to 55.3%) and 6.3% (95% CI, 4.0% to 9.3%). HIV infection, at least 8 years since anal coital debut, concurrency, and external warts were independently statistically associated with SIL.ConclusionProficiency with HRA increased with experience over time. However, HSIL detection rates were low, potentially affected by obstructed views from internal warts and low biopsy rates, highlighting the need for ongoing evaluation and mentoring to validate this finding. HRA is a feasible first-line screening tool at an MSM-friendly health care facility. Years since anal coital debut and external warts could prioritize screening.

Standardized terminology is critical to providing consistent reports to referring clinicians. This lexicon aims to provide a reference for terminology frequently used in rectal cancer and reflects the consensus of the Society of Abdominal Radiology Disease Focused Panel in Rectal cancer. This lexicon divided the terms into the following categories: primary tumor staging, nodal staging, treatment response, anal canal anatomy, general anatomy, and treatments.