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. 2021 Sep 24:11:688615.
doi: 10.3389/fonc.2021.688615. eCollection 2021.

HPV Positive Status Is a Favorable Prognostic Factor in Non-Nasopharyngeal Head and Neck Squamous Cell Carcinoma Patients: A Retrospective Study From the Surveillance, Epidemiology, and End Results Database

Qiuji Wu  1   2   3 , Miao Wang  1   2   3 , Yixin Liu  1   2   3 , Xulong Wang  1   2   3 , Yi Li  1   2   3 , Xiaoyan Hu  1   2   3 , Ye Qiu  1   2   3 , Wenjing Liang  1   2   3 , Yongchang Wei  1   2   3 , Yahua Zhong  1   2   3
Affiliations

HPV Positive Status Is a Favorable Prognostic Factor in Non-Nasopharyngeal Head and Neck Squamous Cell Carcinoma Patients: A Retrospective Study From the Surveillance, Epidemiology, and End Results Database

Qiuji Wu et al. Front Oncol. .

Abstract

Objective: To investigate the impact of the human papillomavirus (HPV) status on head and neck squamous cell carcinoma (HNSCC) arising from different anatomic subsites.

Methods: HNSCC 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.

Results: A 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.

Conclusion: HPV 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.

Keywords: SEER database; head and neck squamous cell carcinoma (HNSCC); human papillomavirus (HPV); nomogram; prognosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Associations between patient characteristics and HPV status. HPV, human papillomavirus.
Figure 2
Figure 2
Impact of HPV infection on the overall survival of HNSCC patients arising from different anatomical subsites. K-M plots of the overall survival were shown for: (A) total population, (B) oropharyngeal carcinoma, (C) hypopharyngeal carcinoma, (D) nasopharyngeal carcinoma. HPV, human papillomavirus; HNSCC, head and neck squamous cell carcinoma; OPC, oropharyngeal carcinoma; HPC, hypopharyngeal carcinoma; NPC, nasopharyngeal carcinoma.
Figure 3
Figure 3
Survival nomograms and risk groups for OPC and HPC patients. (A) Prediction of the 3- and 5-year OS in OPC patients and the risk groups based on the total points of each OPC patient in the training cohort; (B) Prediction of the 3- and 5-year OS in HPC patients and the risk groups based on the total points of each HPC patient in the training cohort. OS, overall survival; OPC, oropharyngeal carcinoma; HPC, hypopharyngeal carcinoma.
Figure 4
Figure 4
ROC curves depicting the predictive performance of the survival nomograms in the training cohorts. (A, B) ROC curves for the 3- and 5-year OS of OPC patients in the training cohort; (C, D) ROC curves for the 3- and 5-year OS of HPC patients in the training cohort. ROC, receiver-operating characteristic; OS, overall survival; FP, false positive; TP, true positive; OPC, oropharyngeal carcinoma; HPC, hypopharyngeal carcinoma.
Figure 5
Figure 5
The calibration curves for predicting the OS of OPC and HPC patients in the training cohorts. (A, B) Calibration curves for the 3- and 5-year OS of OPC patients in the training cohort; (C, D) calibration curves for the 3- and 5-year OS of HPC patients in the training cohort. OS, overall survival; OPC, oropharyngeal carcinoma; HPC, hypopharyngeal carcinoma.
Figure 6
Figure 6
Kaplan–Meier curves of the OS for OPC and HPC patients in the low-, intermediate-, and high-risk groups. (A–C): Kaplan–Meier curves of the OS for OPC patients in the overall, training, and validation cohort; (D–F) Kaplan–Meier curves of the OS for HPC patients in the overall, training, and validation cohort. OS, overall survival; OPC, oropharyngeal carcinoma; HPC, hypopharyngeal carcinoma.
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