Prognostic significance of HPV status in the re-irradiation of recurrent and second primary cancers of the head and neck.

Purpose: To evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field. Methods and materials: The medical records of 54 consecutive patients who underwent re-irradiation for squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of recurrent disease that had previously been treated with doses of radiation therapy of at least 60 Gy were included. Determination of HPV status at the time of recurrence was performed by p16 immunohistochemistry. The median age at re-irradiation was 58.5 years (range, 27.9 to 81.5 years). Thirty patients (55.5%) were lifelong never-smokers. The Kaplan Meier method was used to calculate overall survival, progression-free survival, and local-regional control, and distant metastasis-free survival with comparisons between groups performed using the log-rank test. Results: HPV status among tumors that were re-irradiated was as follows: 16 positive (29.7%); 7 negative (12.9%); 31 unknown (57.4%). The median overall survival in the entire cohort was 11.7 months (range, 8 to 27 months), with the 1-year and 2-year estimates of overall survival being 47.2% and 38.4%, respectively. A statistical trend was identified favoring patients with HPV-positive cancers with respect to the endpoints of overall survival (p = 0.06) and progression-free survival (p = 0.08) after re-irradiation when compared to the HPV-negative/unknown population. There was no significant difference in distant control between the two cohorts (p = 0.40). Conclusions: The favorable prognostic significance of HPV seemingly extends to patients treated by re-irradiation suggesting that this biomarker may be useful in risk stratification in this setting.