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BackgroundMultiple anal human papillomavirus (HPVs) may increase the risk of anal cancer among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). The Jaccard Similarity Index (JSI) was explored as a measure of multiple HPV persistence.MethodsThe TRUST/RV368 cohort enrolled MSM living with and without HIV in Abuja and Lagos, Nigeria. Participants with anal swabs at baseline, 3- and 12-month visits were tested for high- and low-risk HPVs using a next-generation sequencing assay. Persistence of the same HPV genotypes over time was calculated using the JSI and categorized into high, medium, and low similarity tertiles. Factors associated with higher versus lower similarity were estimated with multivariable ordinal logistic regression and reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs).ResultsOf the 225 participants, median age was 25 years (interquartile range, 22-29 years), 62% were living with HIV, median HPVs was 3 (interquartile range, 2-5), and HPV6 (28%), HPV16 (26%), HPV11 (23%), and HPV45 (20%) were most prevalent. Fifty-three percent of participants had highly similar HPVs at 3 months, and the similarity was associated with HIV (aOR, 3.11; 95% CI, 1.6-5.9) and recent receptive sex (aOR, 1.9; 95% CI, 1.0-3.5). By 12 months, 20% had highly similar HPVs, and it was associated with 12 years or longer since anal coital debut (aOR, 6.8; 95% CI, 3.1-5.2), self-reported genital warts (aOR, 3.1; 95% CI, 1.5-6.6), and 200 or less CD4 cells/mm3 (aOR, 13.3; 95% CI, 2.7-65.2) for those living with HIV.ConclusionsStudies evaluating the JSI as a predictor of high-grade intraepithelial lesions would further confirm its applicability as a quantitative measure of multiple HPV persistence.

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.

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.

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.

The development of normal tissue radiation dose-response models for children with cancer has been challenged by many factors, including small sample sizes; the long length of follow-up needed to observe some toxicities; the continuing occurrence of events beyond the time of assessment; the often complex relationship between age at treatment, normal tissue developmental dynamics, and age at assessment; and the need to use retrospective dosimetry. Meta-analyses of published pediatric outcome studies face additional obstacles of incomplete reporting of critical dosimetric, clinical, and statistical information. This report describes general methods used to address some of the pediatric modeling issues. It highlights previous single- and multi-institutional pediatric dose-response studies and summarizes how each PENTEC taskforce addressed the challenges and limitations of the reviewed publications in constructing, when possible, organ-specific dose-effect models. [ABSTRACT FROM AUTHOR]

Background EuroQoL EQ-5D-5L is a commonly used measure of health-related quality of life in clinical trials given the use of its index score as a measure of health utilities. It is unclear whether EQ-5D-5L is sensitive to changes in neurocognitive function and progression that occur following brain radiation. This study sought to evaluate the sensitivity of EQ-5D-5L in reflecting these changes. Methods A secondary analysis of NRG Oncology CC001 was performed. Mean EQ-5D-5L index and visual analog scale (VAS) score changes from baseline between groups of patients stratified by neurocognitive function and intracranial progression status were assessed. MD Anderson Symptom Inventory for brain tumor (MDASI-BT) symptom and interference items were also analyzed between groups. Results EQ-5D-5L mean index and VAS score changes between patients who had cognitive failure and those who had preserved cognition showed no statistically significant differences at any timepoint. In contrast, VAS changes at 4 months (1.61 vs -5.13, P  = .05) and 6 months (8.17 vs −0.14, P  = .04) were significantly improved in the patients who survived without intracranial progression. MDASI-BT cognitive factor scores were improved in the cohort of patients with preserved neurocognitive function at 2 months (1.68 vs 2.08, P  = .05) and 4 months (1.35 vs 1.83, P  = .04). MDASI-BT symptom interference was significantly associated with intracranial progression at 4 months, but not with neurocognitive status. Conclusion EQ-5D-5L index and VAS scores were not sensitive to neurocognitive changes that patients experienced, but VAS scores were sensitive to progression. This study challenges the routine use of EQ-5D as a quality of life metric in brain metastases clinical trials that are focused on preventing neurocognitive dysfunction. Trial Registration NCT# 02360215. [ABSTRACT FROM AUTHOR]