Differential outcome of concurrent radiotherapy plus epidermal growth factor receptor inhibitors versus radiotherapy plus cisplatin in patients with human papillomavirus-related head and neck cancer

• Published in: BMC cancer Vol. 13; no. 1; p. 26
• Main Authors: Pajares, Bella, Trigo, Jose M, Toledo, Maria D, Álvarez, Martina, González-Hermoso, Carlos, Rueda, Antonio, Medina, Jose A, de Luque, Vanessa, Jerez, Jose M, Alba, Emilio
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.01.2013; BioMed Central
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - therapeutic use; Cancer therapies; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - secondary; Carcinoma, Squamous Cell - therapy; Carcinoma, Squamous Cell - virology; Cetuximab; Chemoradiotherapy; Cisplatin - therapeutic use; Complications and side effects; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Disease-Free Survival; DNA, Viral - metabolism; Dose Fractionation; Drug therapy; Epidermal growth factor; Female; Fractionation; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; Head and Neck Neoplasms - virology; Health aspects; Human papillomavirus; Human papillomavirus 16; Human papillomavirus 16 - genetics; Humans; Kaplan-Meier Estimate; Laboratories; Male; Medical prognosis; Medical research; Medicine, Experimental; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local - metabolism; Oncology; Papillomavirus infections; Pathology; Patients; Polymerase chain reaction; Proportional Hazards Models; Quinazolines - therapeutic use; Radiation therapy; Radiotherapy; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Retrospective Studies; Tumors; Spain; Costa del Sol
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-13-26

Human papillomavirus (HPV)-related head and neck cancer has been associated with an improved prognosis in patients treated with radiotherapy (RT) +/- chemotherapy (CT); however, RT combined with epidermal growth factor receptor (EGFR) inhibitors has not been fully studied in this group of patients. Immunohistochemical expression of p16 and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 108 stage III/IV head and neck cancer patients treated with RT+CT (56) or RT+EGFR inhibitors (52). Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. DNA of HPV16 was found in 12 of 108 tumors (11%) and p16 positivity in 18 tumors (17%), with similar rates in both arms of treatment. After a median follow-up time of 35 months (range 6-135), p16-positive patients treated with RT+EGFR inhibitors showed improved survival compared with those treated with RT+CT (2-year OS 88% vs. 60%, HR 0.18; 95% CI 0.04 to 0.88; p = 0.01; and 2-year DFS 75% vs. 47%, HR 0.17; 95% CI 0.03 to 0.8; p = 0.01). However, no differences were observed in p16-negative patients (2-year OS 56% vs. 53%, HR 0.97; 95% CI 0.55 to 1.7; p = 0.9; and 2-year DFS 43% vs. 45%, HR 0.99; 95% CI 0.57 to 1.7; p = 0.9). This is the first study to show that p16-positive patients may benefit more from RT+EGFR inhibitors than conventional RT+CT. These results are hypothesis-generating and should be confirmed in prospective trials.