title: Concurrent radiotherapy plus epidermal growth factor receptor inhibitors in patients with human papillomavirus-related head and neck cancer.
abstract: OBJECTIVE
  Concurrent radio-chemotherapy (RT-CT) is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but RT plus epidermal growth factor receptor (EGFR) inhibitors is an effective option when CT is not appropriate. Human papillomavirus (HPV) is associated with an improved prognosis in LA-HNSCC; however, it has not been fully studied as a prognostic factor after RT + EGFR inhibitors.
  
  
  METHODS
  Immunohistochemical expression of p16INK4A and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 52 stage III/IV LA-HNSCC patients treated with RT + EGFR inhibitors. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method.
  
  
  RESULTS
  DNA of HPV16 was found in six of 52 tumors (12 %) and p16 positivity in eight tumors (15 %). After a median follow-up time of 45 months (6-110), p16-positive patients treated with RT + EGFR inhibitors showed an improved DFS (2-year DFS 75 vs. 44 %, HR 0.25, 95 % CI 0.06-0.99, p = 0.047) compared with p16-negative patients. These differences were outperformed when compared by HPV16 status (2-year OS rates of 83 vs. 58 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049 and 2-year DFS rates of 83 vs. 45 %, HR 0.17, 95 % CI 0.02-0.99, p = 0.049). In the Cox regression analysis with OS as the end point, ECOG 0-1 was the only prognostic factor independently associated with a good prognosis in the multivariable analysis.
  
  
  CONCLUSIONS
  In this study, p16/HPV16-positive patients with LA-HNSCC treated with RT + EGFR inhibitors showed a better survival, not confirmed in multivariate analysis.
authors.affiliation: Department of Medical Oncology, Servicio de Oncología Médica del Hospital Clínico Virgen de la Victoria, Campus Teatinos s/n, 29010, Málaga, Spain, bella.pajares@fundacionimabis.org.
authors.forename: B
authors.initials: B
authors.lastname: Pajares
authors.forename: L
authors.initials: L
authors.lastname: Perez-Villa
authors.forename: J M
authors.initials: JM
authors.lastname: Trigo
authors.forename: M D
authors.initials: MD
authors.lastname: Toledo
authors.forename: M
authors.initials: M
authors.lastname: Alvarez
authors.forename: B
authors.initials: B
authors.lastname: Jimenez
authors.forename: J A
authors.initials: JA
authors.lastname: Medina
authors.forename: V
authors.initials: V
authors.lastname: de Luque
authors.forename: J M
authors.initials: JM
authors.lastname: Jerez
authors.forename: E
authors.initials: E
authors.lastname: Alba
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000628:therapy* / Q000821:virology*; D059248:Chemoradiotherapy / Q000379:methods*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000628:therapy* / Q000821:virology*; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors