title: It is not just IMRT: Human papillomavirus related oropharynx squamous cell carcinoma is associated with better swallowing outcomes after definitive chemoradiotherapy.
abstract: OBJECTIVE
  Long term swallowing dysfunction in patients with oropharynx squamous cell carcinoma (OPSCC) treated with concurrent chemoradiation (CRT) is declining. While the use of intensity modulated radiotherapy (IMRT) is commonly believed to be a potential cause, we hypothesize that the increasing incidence of human papillomavirus (HPV) related disease may also favorably impact this outcome.
  
  
  METHODS
  We reviewed 130 HPV+ and 17 HPV- patients with stage III-IV OPSCC treated exclusively with conventional 3-field radiotherapy with chemotherapy between 2002 and 2010. The rates of normal diet, limited diet (significant restrictions in the types of foods eaten, and/or requiring nutritional supplementation for weight maintenance) and feeding tube dependence (FTD) were compared between HPV+ and HPV- patients. Cox proportional hazards modeling were used to perform univariate analysis (UVA) to examine predictors of a combined endpoint of dietary limitation, which included limited diet and/or FTD. These outcomes were also compared to our previously reported cohort of OPSCC patients treated between 1989 and 2002 to assess changes in toxicity over time given the changing disease epidemiology, in the setting of identical treatment regimens.
  
  
  RESULTS
  With a median follow-up of 55 months, HPV+ patients more frequently had resumed a normal diet (87% vs. 65%) at last follow up and had lower rates of limited diet (9% vs. 18%) and FTD (4% vs. 18%) compared to HPV- patients (p=0.02). HPV status was the only significant predictor of reduced swallowing dysfunction on UVA (HR 0.19; p=0.008). When compared to our 1989-2002 cohort, patients treated between 2002 and 2010 had less FTD (7.5% vs. 34%, p<0.001) and dietary limitations (26% vs.46%, p<0.001) at 6 months post treatment.
  
  
  CONCLUSIONS
  HPV+ patients with OPSCC have reduced late swallowing dysfunction after chemoradiation compared to HPV- patients. The changing epidemiology of OPSCC may play a role in toxicity reduction in these patients, independent of the increasing use of IMRT.
authors.affiliation: Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: M
authors.initials: M
authors.lastname: Naik
authors.affiliation: Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: M C
authors.initials: MC
authors.lastname: Ward
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: T J
authors.initials: TJ
authors.lastname: Bledsoe
authors.affiliation: Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: A M S
authors.initials: AM
authors.lastname: Kumar
authors.affiliation: Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland, OH, United States.
authors.forename: L A
authors.initials: LA
authors.lastname: Rybicki
authors.affiliation: Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: J P
authors.initials: JP
authors.lastname: Saxton
authors.affiliation: Department of Otolaryngology, Head and Neck Institute, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: B B
authors.initials: BB
authors.lastname: Burkey
authors.affiliation: Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: J F
authors.initials: JF
authors.lastname: Greskovich
authors.affiliation: Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States.
authors.forename: D J
authors.initials: DJ
authors.lastname: Adelstein
authors.affiliation: Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, United States. Electronic address: koyfmas@ccf.org.
authors.forename: S A
authors.initials: SA
authors.lastname: Koyfman
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D003680:Deglutition Disorders / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000150:complications / Q000628:therapy*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000628:therapy*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
keywords: 3D-conformal radiation; Human-papillomavirus; Late toxicity; Oropharyngeal cancer