Association of p16^INK4a overexpression with improved outcomes in young patients with squamous cell cancers of the oral tongue

Abstract

Background. The aim of this study was to examine biomolecular profiles in a cohort of young adults with squamous cell cancers (SCCs) of the oral tongue.Methods. We identified all patients aged 18 to 39 years diagnosed with SCC of the oral tongue at our institution. Immunohistochemical (IHC) staining was performed for p16 INK4a , epidermal growth factor receptor (EGFR), phosphorylated-EGFR (pEGFR), p53, and ERCC1. Human papillomavirus (HPV) testing was performed using in situ hybridization (ISH) and polymerase chain reaction (PCR). Biomarker expression and HPV status were correlated with outcomes.Results. We identified 25 patients with sufficient tumor samples. Median age at diagnosis was 30 years (range, 20-39 years). p16INK4a overexpression was observed in 11 of 25 patients, whereas HPV-16 positivity was observed in none of the tumor samples by ISH and 2 of the tumor samples by PCR. p16INK4a positivity was correlated with improved relapse-free survival (hazard ratio [HR] ¼ 0.23, p ¼ .01) and overall survival (HR ¼ 0.28, p ¼ .05). Neither EGFR, pEGFR, p53, nor excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) expression correlated with outcome on univariate analysis.Conclusions. p16 INK4a overexpression was common and was a marker of favorable prognosis. p16INK4a overexpression was not a reliable predictor of HPV positivity in our cohort.

Head and Neck Squamous Cell Carcinoma in Iranian Patients and Risk Factors in Young Adults: a Fifteen-Year Study

“…Genetic factors have also been studied vastly as a risk factor for developing HNSCC in young adults and as a prognosis determinant; while polymorphisms of DNA repair genes have not been established to be responsible for developing the disease in young adults Kostrzewska et al, 2012), over-expression of p16(INK4a) has been found to be associated with favorable prognosis in young patients with SCCs of the oral tongue (Harris et al, 2011) and Pfeiffer et al have found regions of DNA deletions (named germline loss of heterozygosity) that may contribute to genetic susceptibility for HNSCC in young adults and non-smokers (Pfeiffer et al, 2011).…”

Human Papillomavirus Detection in Head and Neck Squamous Cell Carcinomas and Its Clinical Implications

“…It is clear that head and neck squamous cell carcinoma human papillomavirus-positive and p16 expressing is different from classic head and neck squamous cell carcinoma, but it is not clear whether head and neck squamous cell carcinoma human papillomavirus-positive and p16 non expressing (probably, tobacco/alcohol-related tumors that are infected by high-risk human papillomavirus) represents a group biologically distinct from human papillomavirus-negative tumors (Cheng et al, 1995). Other studies in (Smith et al, 2012;Harris et al, 2011) have confirmed better disease-specific and recurrence-free survival in human papillomavirus and/or p16 positive tumors.…”

“…Given that the rate of p53 mutation is quite low in human papillomavirus-associated tumors, the addition of p53 mutation sequencing could have added valuable information had sufficient tissue been available (Harris et al, 2011). There have been conflicting data on p53 expression in human papillomavirus positive head and neck squamous cell carcinoma tumor cells.…”

“…About class IV, several studies (Reimers et al, 2007;Harris et al, 2011;Shah et al, 2009;Weinberger et al, 2004) have shown that patients with human papillomavirus negative and p16 positive tumors had better outcomes than patients with p16 negative tumors. So, p16 status could be the truly important prognostic marker in head and neck squamous cell carcinoma, independent of human papillomavirus infection.…”

“…For all this, p16 positivity has been proposed to be a more reliable and reproducible prognostic marker in head and neck squamous cell carcinoma (Harris et al, 2011).…”