Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer

Palefsky, Joel M.; Lee, Jeannette; Jay, Naomi; Goldstone, Stephen E.; Darragh, Teresa M.; Dunlevy, Hillary A; Rosa-Cunha, Isabella; Arons, Abigail; Pugliese, Julia C; Vena, Don; Sparano, Joseph A.; Wilkin, Timothy; Bucher, Gary; Stier, Elizabeth A.; Gomez, Maribel Tirado; Flowers, Lisa; Barroso, Luis F.; Mitsuyasu, Ronald T.; Lensing, Shelly; Logan, Jeffrey; Aboulafia, David M.; Schouten, Jeffrey T.; Ossa, Juan de la; Levine, Rebecca; Korman, Jessica D; Hagensee, Michael E.; Atkinson, Thomas M.; Einstein, Mark H.; Cracchiolo, Bernadette; Wiley, Dorothy J.; Ellsworth, Grant; Brickman, Cristina; Berry-Lawhorn, J. Michael

doi:10.1056/nejmoa2201048

Cited by 237 publications

(248 citation statements)

References 38 publications

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“…Participants must meet all following inclusion criteria: HIV+ patient at least 18 years of age; cisgender man, transgender man or transgender woman who has sex with men (further referred to as MSM); HGAIN (≥1 lesion) present at the first visit and thereafter confirmed by histopathology; satisfactory HRA at baseline, that is, visualisation of the entire transformation zone with biopsies of all visible lesions. The following exclusion criteria will be applied: HGAIN covering >50% of the circumference of the anal canal (progression to cancer of these patients is estimated to be considerable, and therefore withholding treatment would be unethical)7 26; clinical suspicion of anal cancer; diagnosis/history of anal cancer; treatment for HGAIN in the past 6 months; previous HPV vaccination; concomitant cancer and insufficient Dutch or English language skills. Since the proportion of recurring AIN episodes after treatment in current practice is high (>50% of cases), we will include participants with and without a history of (treatment for) AIN.…”

Section: Methods and Analysismentioning

confidence: 99%

“…A recent large randomized controlled trial has shown a progression rate of HGAIN of 402 per 100,000 personyears (95% confidence interval, 262 to 616) in patients that were actively monitored for HGAIN, and 173 per 100,000 person-years (95% confidence interval, 90 to 332) in the group of patients that was treated for HGAIN. 7 On the other hand, 28% of HGAIN show complete and spontaneous regression within 1 year. [8][9][10] At present, we cannot distinguish between HGAIN likely to regress and HGAIN at risk of progression.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

“…For the sample size calculation we used the following information: the methylation marker panel for AIN3+ detection in HIV+ MSM has an area under the curve (AUC) of 0.89, 25 with 53% of HGAIN being methylation positive at 90% specificity; 30% of HGAIN show spontaneous regression [7][8][9] ; 13% of HGAIN known to regress during follow-up are methylation positive (pilot data).…”

Section: Sample Sizementioning

confidence: 99%

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DNA Methylation Analysis to predict Regression of high-grade anal Intraepithelial Neoplasia in HIV+ men (MARINE): a cohort study protocol

et al. 2022

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IntroductionAnal cancer precursors, or high-grade anal intraepithelial neoplasia (HGAIN), are highly prevalent in HIV-seropositive (HIV+) men who have sex with men (MSM). Around 30% of lesions regress within 1 year, but current histopathological assessment is unable to distinguish between HGAIN likely to regress and HGAIN likely to persist or progress to cancer. We aim to assess if host cell DNA methylation markers can predict regression of HGAIN, thus determining the need for immediate treatment or active surveillance. This could reduce overtreatment and the associated anal and psycho-sexual morbidity.Methods and analysisThis is an active surveillance cohort study in three centres located in Amsterdam, the Netherlands, in 200 HIV+ MSM diagnosed with HGAIN. Participants will not be treated, but closely monitored during 24 months of follow-up with 6 monthly visits including cytology, and high-resolution anoscopy with biopsies. The primary study endpoint is histopathological regression of each baseline HGAIN lesion at the end of the study. Regression is defined as ≤low grade anal intraepithelial neoplasia in the exit biopsy at 24 months. Regression proportions in lesions with low versus high methylation levels (ASCL1, ZNF582), other biomarkers (HPV genotype, HPV-E4, p16INK4A, Ki-67) and immunological markers at baseline will be compared. Main secondary endpoints are the histological and clinical outcome (ie, the number of octants affected by HGAIN) of each baseline HGAIN lesion and overall HGAIN disease (i.e., all lesions combined) after each visit. The health-related quality of life of the study group will be compared with that of a control group of 50 HIV+ MSM receiving regular HGAIN treatment.Ethics and disseminationEthics approval was obtained from the Institutional Review Board of the Academic Medical Center (Amsterdam, The Netherlands; reference no. 2021_099). Participants are required to provide written informed consent. Findings will be disseminated through publication in peer-reviewed scientific journals and presentations at international scientific conferences; dissemination to policy makers and the target patient group will be achieved through our (inter-)national network, professional associations and collaboration with a patient representative organisation.Trial registration numberNL9664.

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Section: Methods and Analysismentioning

confidence: 99%

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

Section: Sample Sizementioning

confidence: 99%

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DNA Methylation Analysis to predict Regression of high-grade anal Intraepithelial Neoplasia in HIV+ men (MARINE): a cohort study protocol

et al. 2022

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“…treatment of precancerous anal lesions in people living with hIV (June 2022) In persons living with HIV, anal high-grade squamous intraepithelial lesions (HSIL) are a risk factor for anal cancer, but whether treatment of HSIL reduces risk has not been tested prospectively. In the ANCHOR trial in which nearly 4500 individuals age ≥35 years with HIV and HSIL were randomly assigned to treatment (ablation, excision, or topical therapy) or active monitoring, treatment reduced the risk of progression to invasive cancer by 57 percent (95% CI 6-80) at a median follow up of 26 months [5]. The rate of treatment-related serious adverse events was low overall (7 of 2227) and included skin ulceration, anal abscess, and treatment-related pain.…”

Section: Cancer Mortality In the United States During The Covid-19 Pa...mentioning

confidence: 99%

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2022

Oncology Times

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UpToDate® and Oncology Times are collaborating to present select content synopses on "What's New in Oncology." UpToDate is an evidence-based, clinical support resource used worldwide by healthcare practitioners to make decisions at the point of care. For complete, current "What's New" content, or to become a subscriber for full content access, go to www.uptodate.com. "What's New" abstract information is free for all medical professionals.

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“…While vaccination against human papillomavirus (HPV) is the primary preventative practice [ 4 , 5 ], secondary prevention has focused on screening for and treating precancerous HPV-associated anal high-grade squamous intraepithelial lesions (HSIL) to prevent progression to cancer [ 6 , 7 ]. In 2014 the US National Cancer Institute (NCI) funded the Phase III Anal Cancer/HSIL Outcomes Research (ANCHOR) randomized controlled trial (clinicaltrials.gov identifier: NCT02135419), which determined that treatment of anal HSIL, versus active monitoring, is effective in reducing incidence of anal cancer in PLWH [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Linguistic validation of the Spanish version of the Anal Cancer High-Grade squamous intraepithelial lesions outcomes Research Health-Related Symptom Index (A-HRSI): AMC-A04

Atkinson

Lynch

Vera

et al. 2022

J Patient Rep Outcomes

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Objectives The Anal Cancer High-grade squamous intraepithelial lesions (HSIL) Outcomes Research (ANCHOR) Health-Related Symptom Index (A-HRSI) is a 25-item measure that assesses physical symptoms and impacts, and psychological symptoms. To promote generalizability and equity in the capture of these concepts in Spanish-speaking participants, we linguistically validated a Spanish version of A-HRSI. Methods Following independent forward translation and reconciliation of A-HRSI from English to Spanish, two rounds of cognitive interviews were completed with ANCHOR participants who had been diagnosed with anal HSIL in the prior nine months and preferred delivery of their healthcare in Spanish. Interviews were coded to highlight any items and concepts that were reported as being difficult for any reason by ≥ 3 participants, with such items revised during a research team panel discussion and tested in a second round of interviews if applicable. Results Seventeen participants representing 8 nationalities were enrolled (Round 1 n=10, Round 2 n=7); 7 participants reported not completing high school (41.2%). No difficulties were reported with respect to the theoretical concepts measured by A-HRSI. We made modifications to the Spanish translation of eight items and two response option terms in cases where participants had difficulty understanding a term, experienced problems in discriminating between terms, or preferred the use of an alternative term to represent the concept(s). Conclusion The Spanish version of A-HRSI is a linguistically valid tool that can be used to assess physical symptoms, impacts, and psychological symptoms related to anal HSIL. Plain English Summary Language is a tremendous barrier to enrolling patients to clinical trials. The anal cancer high-grade squamous intraepithelial lesions (HSIL) outcomes research [ANCHOR] trial is a randomized clinical trial that recently established that the treatment of anal HSIL, versus active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV (PLWH). The ANCHOR Health-Related Symptom Index (A-HRSI) is a 25-item patient-reported outcomes measure that was developed to assess physical symptoms, physical impacts, and psychological symptoms related to anal HSIL. As approximately 10% of ANCHOR participants preferred the delivery of their healthcare in Spanish, the purpose of the present study was to linguistically validate a Spanish version of A-HRSI. Based on feedback from interviews with 17 participants from the ANCHOR trial who had been diagnosed with anal HSIL in the prior nine months and preferred delivery of their healthcare in Spanish, we made modifications to the Spanish translation of eight items and two response option terms in cases where participants had difficulty understanding a term, experienced problems in discriminating between terms, or preferred the use of an alternative term to represent the concept(s). The Spanish version of A-HRSI is a linguistically valid tool that can be used to assess physical symptoms, impacts, and psychological symptoms related to anal HSIL as part of clinical trials or routine care.

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Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer

Cited by 237 publications

References 38 publications

DNA Methylation Analysis to predict Regression of high-grade anal Intraepithelial Neoplasia in HIV+ men (MARINE): a cohort study protocol

DNA Methylation Analysis to predict Regression of high-grade anal Intraepithelial Neoplasia in HIV+ men (MARINE): a cohort study protocol

UpToDate®

Linguistic validation of the Spanish version of the Anal Cancer High-Grade squamous intraepithelial lesions outcomes Research Health-Related Symptom Index (A-HRSI): AMC-A04

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