The prognostic value of HPV status and p16 expression in patients with carcinoma of the anal canal

• Published in: PloS one Vol. 9; no. 10; p. e108790
• Main Authors: Roldán Urgoiti, Gloria B, Gustafson, Karla, Klimowicz, Alexander C, Petrillo, Stephanie K, Magliocco, Anthony M, Doll, Corinne M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2014; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Alphapapillomavirus - classification; Alphapapillomavirus - genetics; Anal cancer; Anus; Anus Neoplasms - genetics; Anus Neoplasms - mortality; Anus Neoplasms - pathology; Anus Neoplasms - virology; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor; Canals; Canals (anatomy); Cancer; Chemoradiotherapy; Colorectal cancer; Correlation analysis; Correlation coefficient; Correlation coefficients; Cyclin-Dependent Kinase Inhibitor p16; Deoxyribonucleic acid; DNA; Electrolytes; Female; Gene Expression; Genotype; Genotypes; Health risks; Human papillomavirus; Humans; Immunohistochemistry; Infections; Male; Medical prognosis; Medicine and Health Sciences; Middle Aged; Molecular modelling; Neoplasm Metastasis; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Oncology; Papillomavirus Infections - complications; Paraffin; Patient Outcome Assessment; Patients; Pretreatment; Prognosis; Protein expression; Proteins; Radiation therapy; Risk groups; Squamous cell carcinoma; Test procedures; Tumor Burden; Tumors; Canada; Calgary Alberta Canada; Alberta Canada; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0108790

In anal cancer studies, the detection frequency of high-risk HPV (human papillomavirus) is variable, depending on the method used. There are limited data reporting results of different HPV detection techniques in the same clinical series, and very few correlating results with clinical outcome. To evaluate tumor expression of p16/HPV16 using three different methods, and to determine their association with clinical outcome in patients with anal canal squamous cell carcinomas (SCC). This retrospective study included patients with anal canal SCC treated with definitive radiotherapy or chemoradiotherapy at a single institution between 1992 and 2005. Formalin-fixed paraffin-embedded tumor samples from 53 of the 89 (60%) patient pre-treatment biopsies were adequate for tissue microarray construction. HPV status was determined using: p16 expression by conventional immunohistochemistry (IHC) and quantitative IHC (AQUA), HPV genotype analysis by chromogenic in situ hybridization (CISH) and HPV linear array sub-typing. Expression status was correlated with clinical outcome. 80% (28/35) of patient tumors had high p16 expression using conventional IHC. HPV16 CISH was positive in 81% (34/42) of tumors, and 78% (28/36) of tumors were HPV subtype 16. HPV16 CISH correlated with p16 evaluated by conventional IHC (correlation coefficient 0.46; p = 0.01) and by p16 AQUA score (correlation coefficient 0.49; p = 0.001). A subset of cases (15%) had very high p16 quantitative IHC scores (>244) and were associated with a higher incidence of local or distant recurrence (p = 0.04). The vast majority (80%) of anal canal SCC in our series were positive for HPV16/p16, regardless of the testing method used. The exploratory analysis of automated quantitative IHC scoring was the only technique to define a subset of patients with a worse prognosis by p16 expression status on univariate analysis. Further exploration of the molecular mechanisms of treatment resistance in association with very high p16 expression is warranted.