Frequency and prognostic significance of p16INK4A protein overexpression and transcriptionally active human papillomavirus infection in laryngeal squamous cell carcinoma

Abstract

Background:Human papillomavirus (HPV) infection is a powerful prognostic biomarker in a subset of head and neck squamous cell carcinomas, specifically oropharyngeal cancers. However, the role of HPV in non-oropharyngeal sites, such as the larynx, remains unconfirmed.Methods:We evaluated a cohort of 324 laryngeal squamous cell carcinoma (LSCC) patients for the expression of p16INK4A (p16) protein by immunohistochemistry (IHC) and for high-risk HPV E6 and E7 mRNA transcripts by RNA in situ hybridisation (ISH). p16 expression and HPV status were correlated with clinicopathological features and outcomes.Results:Of 307 patients assessable for p16 IHC, 20 (6.5%) were p16 positive. Females and node-positive patients were more likely to be p16 positive (P<0.05). There were no other significant clinical or demographic differences between p16-positive and -negative cases. There was no difference in overall survival (OS) between p16-positive and -negative patients with 2-year survival of 79% in each group (HR=0.83, 95% CI 0.36–1.89, P=0.65). There was no statistically significant difference in failure-free survival (FFS) with 2-year FFS of 79% and 66% for p16-positive and -negative patients, respectively (HR=0.60, 95% CI 0.26–1.36, P=0.22). Only seven cases were found to be HPV RNA ISH positive, all of which were p16 IHC positive. There was no statistically significant difference in OS between patients with HPV RNA ISH-positive tumours compared with -negative tumours with 2-year survival of 86% and 71%, respectively (HR=0.76, 95% CI 0.23–2.5, P=0.65). The 2-year FFS was 86% and 59%, respectively (HR=0.62, 95% CI 0.19–2.03, P=0.43).Conclusions:p16 overexpression is infrequent in LSCC and the proportion of cases with high-risk HPV transcripts is even lower. There are no statistically significant correlations between p16 IHC or HPV RNA ISH status and OS or disease outcomes.

Prevalence and Prognostic Significance of HPV in Laryngeal Squamous Cell Carcinoma in Northeast China

“…Recent reports suggest that p16 is not a reliable predictor of prognosis in LSCC. Young et al analyzed the clinical outcome of patients with LSCC stratified on the basis of p16 expression and concluded that there was no survival advantage among p16+ patients [31]. Consistent with most of the previous findings, our study suggests that HPV infection status is a more reliable surrogate marker than p16 for predicting survival in patients with LSCC.…”

P16 Expression Independent of Human Papilloma Virus in Egyptian Patients with Head and Neck Squamous Cell Carcinoma: A Retrospective Study

“…The authors concluded that positive HVP 16 and/or p16 have no prognostic value on treatment outcome of non-OPSCC. This is consistent with our findings, and several reports suggesting that p16 and /or HPV are not predictors of survival among LSCC [44], [28] and HPSCC [28]. Meshman et al [23] did not support p16 predicting for locoregional control or ORS in the larynx or hypopharynx.…”

“…Other retrospective studies of p16 in LSCC and HSCC agreed with the negative impact of p16 on outcome [44][45][46]. On the contrary, the pooled RTOG analysis of non-OPSCC by Chung et al [16] identified the positive prognostic role of p16 in combined subset analysis.…”

Prognostic significance of non-HPV16 genotypes in oropharyngeal squamous cell carcinoma

“…The authors concluded that validation of these results specifically in OPSCC patients is warranted to inform treatment decisions. Although we also see a significant association by HPV genotype across all sites (results not shown), we concentrated on OPSCC since the prognostic value of HPV status in non-oropharynx tumors has yet to be established [14, 15]. Two other groups in the United States conducted studies comparing HPV genotypes in OPSCC.…”