Laser capture microdissection as a tool to evaluate human papillomavirus genotyping and methylation as biomarkers of persistence and progression of anal lesions. Issue 8 (26th August 2015)

• Record Type: Journal Article
• Authors: Cornall, Alyssa M; Roberts, Jennifer M; Molano, Monica; Machalek, Dorothy A; Phillips, Samuel; Hillman, Richard J; Grulich, Andrew E; Jin, Fengyi; Poynten, I Mary; Templeton, David J; Garland, Suzanne M; Tabrizi, Sepehr N
• Other Names: author non-byline.; Acraman Brian author non-byline.; Prestage Garrett author non-byline.; Crampton Leonie author non-byline.; McGrath Patrick author non-byline.; Petoumenos Kathy author non-byline.; O'Dwyer Matthew author non-byline.; Mellor Robert author non-byline.; Pezzopane Piero author non-byline.; Law Matthew author non-byline.; Law Carmella author non-byline.; Tong Winnie author non-byline.; Seeds Daniel author non-byline.; Fraissard Eddie author non-byline.; Carr Andrew author non-byline.; Varma Rick author non-byline.; Fairley Kit author non-byline.; McCaffery Kirsten author non-byline.; Howard Kirsten author non-byline.; Farnsworth Annabelle author non-byline.; Richards Adele author non-byline.; Thurloe Julia author non-byline.; Feeney Lance author non-byline.; Gluyas Russ author non-byline.
• Is Part Of: BMJ open. Volume 5:Issue 8(2015)
• Publication Date: 2015-08-26
• Subjects: Human papillomavirus -- Anal cancer -- Biomarkers -- Precancerous conditions -- Laser capture microdissection -- HSIL/HGAIN; Medicine -- Research -- Periodicals; 610.72
• DOI: 10.1136/bmjopen-2015-008439
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : Introduction: Anal squamous cell carcinoma is preceded by persistent infection with high-risk human papillomavirus (HPV) and the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). Detection of specific HPV genotypes and HPV-related biomarkers may be an option for primary anal screening. However, more data on the natural history of HPV-related anal lesions are required. The outcomes from this study will enhance our understanding of the clinical and biological behaviour of HPV-related anal lesions and inform the development of future HPV genotype and/or biomarker screening tests. Methods and analysis: HIV-negative and HIV-positive men who have sex with men, aged 35 years and over, recruited from community-based settings in Sydney, Australia, attend 6 clinic visits over 3 years. At the first 5 visits, participants undergo a digital anorectal examination, an anal swab for HPV genotyping and anal cytology, and high-resolution anoscopy with directed biopsy of any visible abnormalities that are suggestive of any abnormality suspicious of SIL. Tissue sections from participants diagnosed with histologically confirmed HSIL at the baseline clinic visit will undergo laser capture microdissection, HPV detection and genotyping, and quantitation of CpG methylation in baseline and follow-up biopsies. Histological and cytological findings in combination with HPV genotyping data will be used to identify persistent HSIL. HSIL will be stratified as non-persistent and persistent based on their status at 12 months. The performance of HPV genotype and methylation status in predicting disease persistence at 12 months will be assessed, along with associations with HIV status and other covariates such as age. Ethics and dissemination: The St Vincent's Hospital Ethics Committee granted ethics approval for the study. Written informed consent is obtained from all individuals before any study-specific procedures are performed. Findings from this study will be disseminated to participants and the community through study newsletters, and through peer-reviewed publications and international conferences.