Detailed Analysis of Clinicopathologic Factors Demonstrate Distinct Difference in Outcome and Prognostic Factors Between Surgically Treated HPV-Positive and Negative Oropharyngeal Cancer

Abstract

Background: Oropharyngeal cancers (OPC) secondary to human papillomavirus (HPV) infections likely represent a completely different disease compared with conventional head and neck cancers. Our objective was to analyze a surgically treated cohort to determine predictors of outcome in HPV-positive versus HPV-negative patients.

Methods: HPV positivity was inferred based on p16-immunohistochemistry. Data was available for 201 patients with OPC treated with surgical resection with/without adjuvant radiotherapy between 1985 and 2005. Subsite distribution was: 66 (33 %) tonsil, 46 (23 %) soft palate, and 89 (44 %) tongue base. Patients were classified into low-, intermediate-, and high-risk groups based on p16 status and smoking history. Outcomes stratified by p16 status and risk groups were determined by the Kaplan-Meier method. Factors predictive of outcome were determined by univariate and multivariate analyses.

Results: In this cohort, 30 % had locally advanced disease (pT3/T4) and 71 % had nodal metastasis. The 5-year overall (OS), disease-specific, and recurrence-free survival rates were 60, 76, and 66 %, respectively. There were 22 % low-, 34 % intermediate-, and 44 % high-risk patients. Patients who were p16-positive had better survival compared with p16-negative (OS, 74 vs. 44 %; p < .001). Similarly, low-risk group patients had a better survival compared with intermediate- and high-risk groups (OS, 76, 68, 45 %, respectively, p < .001). Independent predictors of survival in p16-negative patients included margin status, lymphovascular invasion, pN status, and extracapsular spread. In contrast, none of these were predictive in p16-positive patients.

Conclusions: Surgically treated patients with p16-positive OPC have superior survival compared with p16-negative patients. Outcomes in p16-positive and p16-negative OPC are determined by different prognostic factors supporting the notion that these are very different diseases. These should be incorporated into future clinical trials design.

FIG. 1

Kaplan-Meier plots showing overall (OS) and disease-specific (DSS) survival stratified by p16 status (a) and stratified by risk group category (b). p values based on log-rank test

FIG. 2

Kaplan-Meier plots showing impact of prognostic factors on disease-specific survival (DSS) in p16-positive and p16-negative patients: a pT classification. b pN classification. c Margin status. d Extracapsular spread (ECS). 5-year DSS and p values based on log-rank test