Long-Term Survival and Recurrence in Oropharyngeal Squamous Cell Carcinoma in Relation to Subsites, HPV, and p16-Status

Abstract

Long-term survival data in relation to sub-sites, human papillomavirus (HPV), and p16INK4a (p16) for patients with oropharyngeal squamous cell carcinoma (OPSCC) is still sparse. Furthermore, reports have indicated atypical and late recurrences for patients with HPV and p16 positive OPSCC. Therefore, we assessed long-term survival and recurrence in relation to oropharyngeal subsite and HPV/p16 status. A total of 529 patients with OPSCC, diagnosed in the period 2000–2010, with known HPVDNA and p16-status, were included. HPV/p16 status and sub-sites were correlated to disease-free and overall survival (DFS and OS respectively). The overexpression of p16 (p16+) is associated with significantly better long-term OS and DFS in tonsillar and base of tongue carcinomas (TSCC/BOTSCC), but not in patients with other OPSCC. Patients with HPVDNA+/p16+ TSCC/BOTSCC presented better OS and DFS compared to those with HPVDNA−/p16− tumors, while those with HPVDNA−/p16+ cancer had an intermediate survival. Late recurrences were rare, and significantly more frequent in patients with p16− tumors, while the prognosis after relapse was poor independent of HPVDNA+/−/p16+/− status. In conclusion, patients with p16+ OPSCC do not have more late recurrences than p16−, and a clear prognostic value of p16+ was only observed in TSCC/BOTSCC. Finally, the combination of HPVDNA and p16 provided superior prognostic information compared to p16 alone in TSCC/BOTSCC.

HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management

“…Despite this lack of guideline recognition, anatomical location remains important because SCCs of the tonsils or base of the tongue are more frequently HPV + than those at other sites. Indeed, the prevalence of HPV infection in these sites seems to be lower, with approximately 19–22% of tumours testing positive for HPV, compared with 56–70% for OPSCCs located in the tonsils or base of the tongue 185 , 186 . Furthermore, the prognostic value of HPV infections outside these two anatomical locations seems to be less robust, calling into question the appropriateness of the current AJCC staging system for SCCs at these sites 186 .…”

“…Indeed, the prevalence of HPV infection in these sites seems to be lower, with approximately 19–22% of tumours testing positive for HPV, compared with 56–70% for OPSCCs located in the tonsils or base of the tongue 185 , 186 . Furthermore, the prognostic value of HPV infections outside these two anatomical locations seems to be less robust, calling into question the appropriateness of the current AJCC staging system for SCCs at these sites 186 . These considerations warrant continued investigation of more comprehensive, and potentially more accurate, prognosticators that incorporate the effects of subsite as well as patient history, with particular regard to smoking history as discussed above, on top of current AJCC staging.…”

Tumor Cell Extrinsic Synaptogyrin 3 Expression as a Diagnostic and Prognostic Biomarker in Head and Neck Cancer

“…It is important to note that we were unable to perform ddPCR on all the tumor blocks due to biospecimen availability, which likely negatively influenced our ROC curve analyses; and increasing the number of samples is predicted to strengthen the sensitivity and specificity measures. We note that p16 is a prognostic marker in its own right, regardless of HPV status (26,39,79,(146)(147)(148)(149)(150)(151)(152), and our survival analyses did not correct for that. Therefore, these findings could be strengthened by expanding to a larger and more inclusive HNSCC patient cohort.…”

High-Risk Human Papillomavirus and Epstein–Barr Virus Coinfection: A Potential Role in Head and Neck Carcinogenesis

“…Etiologically, two different types of OPSCCs have been described: HPV-driven and HPV-negative carcinomas, characterized by a distinct biological and clinical behavior [ 92 ]. In fact, patients with HPV-driven OPSCCs usually show a better prognosis compared to those with HPV-negative tumors [ 93 , 94 ]. Furthermore, patients with HPV16-driven OPSCC showed an increased overall survival rate when compared to patients with non-HPV16-positive carcinomas [ 95 ].…”