title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Medical Oncology, University Hospital Virgen de la Victoria, Málaga, Spain. bella.pajares@fundacionimabis.org
authors: Bella
authors: B
authors: Pajares
authors: Jose M
authors: JM
authors: Trigo
authors: Maria D
authors: MD
authors: Toledo
authors: Martina
authors: M
authors: Álvarez
authors: Carlos
authors: C
authors: González-Hermoso
authors: Antonio
authors: A
authors: Rueda
authors: Jose A
authors: JA
authors: Medina
authors: Vanessa
authors: V
authors: de Luque
authors: Jose M
authors: JM
authors: Jerez
authors: Emilio
authors: E
authors: Alba
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000556:secondary / Q000628:therapy* / Q000821:virology; D000068818:Cetuximab; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000627:therapeutic use; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy* / Q000821:virology; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D000077544:Panitumumab; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D011799:Quinazolines; D000077544:Panitumumab; D066246:ErbB Receptors; D000068818:Cetuximab; D002945:Cisplatin; D000077156:Gefitinib