Abstract

ObjectiveTo investigate the impact of the human papillomavirus (HPV) status on head and neck squamous cell carcinoma (HNSCC) arising from different anatomic subsites.MethodsHNSCC patients with known HPV status from the Surveillance, Epidemiology, and End Results (SEER) database between 2010–2015 were included in our analysis. Patients were classified into three categories of HNSCC according to Site recode ICD-O-3/WHO 2008 and Primary Site-labeled, namely, oropharynx, hypopharynx, and nasopharynx. Logistic regression model was conducted to evaluate the relationship between patient characteristics and HPV status. Kaplan-Meier methods and COX regression analysis were used to analyze survival data.ResultsA total of 9,943 HNSCC patients with known HPV status from the SEER database were enrolled, with 6,829 (68.7%) HPV-positive patients. HPV-positive and HPV-negative HNSCC were distinct and had different clinical and socioeconomic features (all P < 0.001). Primary sites, socioeconomical factors (age, sex, marital status, and race), and pathological features (TNM stage and grade) were closely related with HPV status (all P < 0.001). HPV-positive status was a favorable prognostic marker in HNSCC patients with cancers of the oropharynx and hypopharynx (all P < 0.001), but was not in nasopharyngeal carcinoma patients (P = 0.843). A total of 8,933 oropharyngeal carcinoma (OPC) and 558 hypopharyngeal carcinoma (HPC) patients were divided into the training and validation cohorts with a ratio of 1:1. Significant prognostic factors of the OS yielded by multivariate COX analysis in the training cohort were integrated to construct nomograms for OPC and HPC patients. The prognostic models showed a good discrimination with a C-index of 0.79 ± 0.007 and 0.73 ± 0.023 in OPC and HPC, respectively. Favorable calibration was reflected by the calibration curves. Additionally, corresponding risk classification systems for OPC and HPC patients based on the nomograms were built and could perfectly classify patients into low-risk, intermediated-risk, high-risk groups. OS in the three risk groups was accurately differentiated and showed a good discrimination.ConclusionHPV positivity was associated with an improved survival in HNSCC patients with cancers of the oropharynx and hypopharynx. Nomograms and corresponding risk classification systems were constructed to assist clinicians in evaluating the survival of OPC and HPC patients.

Highlights

  • Head and neck squamous cell carcinomas (HNSCC) are an atomically heterogeneous group of neoplasms arising from the nasopharynx, oral cavity, oropharynx, hypopharynx, and larynx

  • A total of 9,943 HNSCC patients with known human papillomavirus (HPV) status from the SEER database were enrolled in this study, including 6,829 (68.7%) HPV-positive patients and 3,114 (31.3%) HPVnegative patients

  • We aimed to determine the role of tumor HPV status in HNSCC from different subsites, based on the customized SEER Head and Neck with HPV Status Database

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Summary

Introduction

Head and neck squamous cell carcinomas (HNSCC) are an atomically heterogeneous group of neoplasms arising from the nasopharynx, oral cavity, oropharynx, hypopharynx, and larynx. There are approximately 700,000 new cases and 380,000 deaths of HNSCC worldwide [1]. It is well known that tobacco smoking, alcohol consumption, and betel quid chewing in Iran and some Southeast Asian countries are classical etiological factors for HNSCC development [2, 3]. Virus infection is another important etiological cause of HNSCC. It has become clear that high-risk human papillomavirus (HPV) infection is an important etiological and prognostic factor for a subset of HNSCC over the last decade [5,6,7]. There is a solid epidemiological work showing that HPV-related HNSCC is on the rise in the Western world with an increased incidence of HPV infection in HNSCC of approximately 50%, while a decrease in incidence of smoking-related HNSCC is seen due to an effective smoking control [8, 9]

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