Human Papillomavirus and Overall Survival After Progression of Oropharyngeal Squamous Cell Carcinoma

SUMMARY: The CDC estimates that more than 2,370 new cases of Human Papilloma Virus (HPV) associated Oropharyngeal Squamous Cell Carcinomas (OPSCC) are diagnosed in women and nearly 9,356 are diagnosed in men each year in the United States and this has been on the rise. Recent studies have shown that over 70% of the OroPharyngeal Squamous Cell Carcinomas (OPSCC) are caused by HPV and HPV-16 is the predominant type present in the tumor cells. The malignant behavior of these tumors is dependent on the expression of viral E6 and E7 oncoproteins that inactivate the tumor suppressor proteins p53 and the retinoblastoma protein (pRb), respectively. HPV-positive OroPharyngeal Squamous Cell Carcinoma (OPSCC) is more common among never smokers or light smokers and patients tend to be younger with better performance status. To address this further, the authors examined the influence of tumor HPV status (tumor p16) on patterns of failure and survival after disease progression, by performing a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression, amongst patients enrolled in the Radiation Therapy Oncology Group (RTOG) trials 0129 and RTOG 0522. Eligible patients from these two trials had stage III-IV OroPharygeal Squamous Cell Carcinoma. Their tumor p16 status was known and these patients had local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy. Of the 181 patients included in this analysis, 105 patients had p16 positive OPSCC and 76 patients had p16 negative OPSCC. Tumor p16 expression was evaluated using immunohistochemistry methodology. Even though the patterns of failure and median time to progression were similar for patients with p16-positive and p16-negative tumors, after a median follow up period of 4 years after disease progression, patients with p16-positive OPSCC had significantly improved Overall Survival (OS) rates compared with p16-negative patients (2-year OS, 54.6% vs 27.6%; median, 2.6 vs 0.8 years; P <0.001). This meant that patients with HPV positive recurrent OPSCC had nearly twice the overall survival rate compared to HPV negative patients. Further, salvage surgery after disease progression in HPV positive patients reduced the risk of death. Factors associated with improved survival in multivariate analysis included, HPV positive status, salvage surgery, locoregional progression vs distant progression, lower T stage at enrollment and less than 20 pack year smoking history. The authors concluded that patients with HPV positive OroPharyngeal Squamous Cell Carcinoma (OPSCC) have tumors with different molecular behavior, compared to HPV negative and tobacco related OPSCC and tumor p16 status is independently associated with Overall Survival among OPSCC patients with disease progression. This important information should be a stratification factor for clinical trials and the benefits of salvage surgery dictates close surveillance as these patients are followed up. Fakhry C, Zhang Q, Nguyen-Tan PF, et al. Published Ahead of Print on June 23, 2014 as 10.1200/JCO.2014.55.1937