title: Human papillomavirus-associated head and neck squamous cell carcinoma survival: a comparison by tumor site and initial treatment.
abstract: Recent evidence suggests that human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) patients have better survival than HPV-negative patients. However, it is unclear if similar patterns for survival exist across different tumor sites, and whether HPV-associated prognosis is modified by type of treatment. We prospectively tested 222 histologically confirmed HNSCC primary tumors for HPV DNA by PCR and HPV E6/E7 RNA by RT-PCR prior to treatment at a large urban health center. Cox proportional hazard ratio models were constructed to assess HPV-associated differences in overall and disease-specific survival adjusting for clinical and demographic covariates. HPV detection varied significantly by primary HNSCC tumor site, from 35 % for oropharynx, to 25 % for hypopharynx, 5 % for larynx, and 3 % for oral cavity (p < 0.0001), with HPV16 accounting for the majority (95 %) of HPV-positive tumors. The hazard-risk of overall and disease-specific death comparing HPV16-positive versus negative oropharyngeal HNSCC was reduced by 74 and 89 %, respectively (p values < 0.05), and was independent of other prognostic indicators; no statistically significant changes in outcomes were observed for non-oropharyngeal HNSCC sites. Prediction of overall survival was better with combined DNA and RNA HPV16 positive PCR detection. There was no difference in HPV16-associated survival whether patients received either surgery or (chemo)radiotherapy as their initial treatment modality. Improved HPV-associated HNSCC survival is limited to patients with oropharyngeal primaries. No selective treatment advantage is observed for HPV-positive tumors, although clinical trials are needed to evaluate which treatment modalities provide the most benefit for HPV-positive HNSCC.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10641, USA.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Salazar
authors.forename: Richard V
authors.initials: RV
authors.lastname: Smith
authors.forename: Madhur K
authors.initials: MK
authors.lastname: Garg
authors.forename: Missak
authors.initials: M
authors.lastname: Haigentz
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Schiff
authors.forename: Nicole
authors.initials: N
authors.lastname: Kawachi
authors.forename: Nicole
authors.initials: N
authors.lastname: Anayannis
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Belbin
authors.forename: Michael B
authors.initials: MB
authors.lastname: Prystowsky
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology* / Q000628:therapy / Q000821:virology; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019647:Oral Surgical Procedures; D030361:Papillomavirus Infections / Q000150:complications* / Q000401:mortality*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D011878:Radiotherapy; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000970:Antineoplastic Agents