Second Primary Head and Neck Malignancies in Patients With Prior Human Papilloma Virus (HPV) Associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) Treated With Radiation

Abstract

The outcomes of second primary head and neck malignancies in survivors of HPV associated OPSCC treated with radiation have not been well documented. The purpose of this study was to review the rate, management, and outcomes of non-metastatic second head and neck malignancies in patients with a history of HPV positive OPSCC treated with definitive or postoperative radiation (RT).This is a single institution IRB approved retrospective study of patients with HPV positive OPSCC treated from 2001-2017 with definitive radiation and at least 3 years of follow up. Diagnoses were considered to be a second head and neck malignancy if they were distinct from index OPSCC with the exclusion of a primary or regional recurrence, primary site > 2 cm from the index OPSCC, and occurred at least 2 years from prior RT. Patients with second malignancies involving the thyroid were excluded. Actuarial analysis was used to calculate overall survival and disease control rates.There were a total of 418 patients who met inclusion criteria with a median follow up of 88.5 months (50.9-150.9 months). A total of 11 patients (2.6%) developed a second primary malignancy in the head and neck (2 larynx, 1 nasal cavity, 6 oral cavity and 2 oropharynx) and all were treated with definitive surgery. Median time between first and second cancers was 73 months (25-123 months). Median follow up for these patients was 25.4 months (7.7-69 months) and the median age at second malignancy was 65 years (range 54-73 years). 64% of patients were former smokers (quit > 3 months) and 36% were never smokers. Pathological tumor stage of the second cancer was T1 in 36%, T2 in 27%, T4a in 36%. The histology was squamous cell carcinoma in 9 patients, spindle cell squamous carcinoma in 1 patient, and adenosquamous carcinoma 1 patient. HPV status was negative in 45.5%, positive in 18.2% and unknown in 36.4%. Post-operative re-irradiation was given in 55%, of which 50% received concurrent chemotherapy. Locoregional control rates at 12 and 24 months were 100% and 62.5% (95% CI: 28.9-96.1%), respectively. Of the 2 patients with local failure, which occurred at 18 and 33 months after diagnosis, salvage therapy with surgery was successful. Regional failure was diagnosed in 2 patients at 13 and 16 months after diagnosis, and both of these patients ultimately died as a result of regional failure. There were no distant failures. One additional patient had died at last follow up which was unrelated to cancer. Estimated 2-year overall survival from the second head and neck malignancy was 78.9% (95% CI: 53.0-100%).The risk of a second head and neck malignancy in survivors of HPV associated OPSCC is low, but as the incidence of HPV related OPSCC remains elevated and the likelihood of cure is excellent, secondary malignancy is an important long-term risk. Despite prior RT, consideration of post-operative re-irradiation is important as regional failure may carry a poor prognosis.