Open Access Research article

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

Bella Pajares1*, Jose M Trigo1, Maria D Toledo2, Martina Álvarez3, Carlos González-Hermoso4, Antonio Rueda5, Jose A Medina2, Vanessa de Luque6, Jose M Jerez7 and Emilio Alba1

Author Affiliations

1 Department of Medical Oncology, University Hospital Virgen de la Victoria, Málaga, Spain

2 Department of Radiotherapy, University Hospital Virgen de la Victoria, Málaga, Spain

3 Department of Pathology, University Hospital Virgen de la Victoria, Málaga, Spain

4 Hospital Costa del Sol, Department of Pathology, Marbella, Málaga, Spain

5 Hospital Costa del Sol, Department of Medical Oncology, Marbella, Málaga, Spain

6 Biomedical Research Laboratory Hospital Virgen de la Victoria, Málaga, Spain

7 Computational Languages Department, Málaga University, Málaga, Spain

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BMC Cancer 2013, 13:26  doi:10.1186/1471-2407-13-26

Published: 18 January 2013



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.

Head and neck cancer; Human papillomavirus; Chemotherapy; Radiotherapy; EGFR inhibitors