p16INK4A, p53, EGFR expression and KRAS mutation status in squamous cell cancers of the anus: Correlation with outcomes following chemo-radiotherapy

Abstract

p16(INK4A) is strongly associated with relapse in SCC of the anus and identifies patients with very poor rates of relapse-free and overall survival. Primary and recurrent anal cancer expresses wild type KRAS, unaffected by treatment, supporting trials targeting EGFR in poor risk/recurrent anal cancer.

High-sensitivity human papilloma virus genotyping reveals near universal positivity in anal squamous cell carcinoma: Different implications for vaccine prevention and prognosis

“…Similar patterns are noted for cervical carcinoma [21]. A number of studies are emerging in which HPV positivity and/or p16 expression are prognostic for improved survival in patients with ASCC treated by CRT [17,[22][23][24].…”

“…First and last slides of each tissue block underwent pathological review (Chakrabarty) to verify the presence of ASCC. Immunohistochemical scores for p16 were recorded as described by the present investigators [17].…”

“…Differences in the transformation activity and progression of HPV may be attributed to allelic variations of E regions [15] -for example, L83V (corresponding to European variant T350G), may be associated with disease progression [16]. pRb is a negative regulator of the cyclin-dependent kinase inhibitor p16 INK4A (p16), such that expression of p16 is a surrogate biomarker of HPV infection [17]. HPV positivity and/or p16 expression in oropharyngeal cancers are associated with a distinct phenotype with good prognosis and complete response to CRT [18][19][20].…”

Human papillomavirus DNA load and p16INK4aexpression predict for local control in patients with anal squamous cell carcinoma treated with chemoradiotherapy

“…As p16 INK4A has been reported to be further regulated by epigenetic control and multiple transcription factors or gain of function in chromosome 11q, 48 it is likely that HPV-negative and HPV-positive anal cancers with low viral load share comparable genetic alterations or epigenetic methylation profiles that might result in reduced sensitivity to RT/CRT and worse prognosis. 32,49,50 We would like to acknowledge the limitations of our study. Although the patient number is relatively large (n 5 95), these data need to be validated prospectively in a larger patient cohort.…”

Prognostic relevance of human papillomavirus infection in anal squamous cell carcinoma: analysis of the national cancer data base

“…There have been prior single institutional, retrospective studies investigating the relevance of HPV infection in ASCC, but most of these reports included a limited number of patients ranging from 47 to 153 patients (20)(21)(22)(23). To that end, the present study was designed to answer that question with an amplified statistical power in a multi-institutional setting by utilizing the large, prospectively acquired, National Cancer Data Base (NCDB) which captures approximately 70% of all malignancies in the United States.…”