title: Retrospective analysis of the impact of HPV status and smoking on mucositis in patients with oropharyngeal squamous cell carcinoma treated with concurrent chemotherapy and radiotherapy.
abstract: OBJECTIVE
  The standard concurrent radiotherapy and chemotherapy regimens for patients with oropharyngeal cancer are highly toxic. Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has recently emerged as a distinct biological and clinical entity with improved response to treatment and prognosis. A tailored therapeutic approach is needed to optimize patient care. The aim of our study was to investigate the impact of HPV and smoking status on early toxicities (primarily mucositis) associated with concurrent chemotherapy and radiotherapy in patients with OPSCC.
  
  
  METHODS
  We retrospectively evaluated 72 consecutive patients with OPSCC and known HPV status treated with concurrent radiotherapy and chemotherapy at our institution. Treatment-related toxicities were stratified by smoking and HPV status and compared using univariate and multivariate logistic regression.
  
  
  RESULTS
  HPV-positive patients had a 6.86-fold increase in the risk of having severe, grade 3-4 mucositis. This effect was preserved after adjusting for patient smoking status, nodal stage, radiotherapy technique and radiotherapy maximum dose. Additionally, HPV status had significant effect on the objective weight loss during treatment and at three months after treatment. Consistently, non-smokers had a significant 2.70-fold increase in the risk of developing severe mucositis.
  
  
  CONCLUSIONS
  Risk factors for OPSCC modify the incidence of treatment-related early toxicities, with HPV-positive and non-smoking status correlating with increased risk of high grade mucositis and associated outcomes. Retrospective single-institution studies need to be interpreted cautiously. However, this finding is important to consider when designing therapeutic strategies for HPV-positive patients and merits further investigation in prospective clinical trials.
authors.affiliation: Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157, USA. Electronic address: mvatca@wakehealth.edu.
authors.forename: M
authors.initials: M
authors.lastname: Vatca
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: jolucas@wakehealth.edu.
authors.forename: J T
authors.initials: JT
authors.lastname: Lucas
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: jlaudadio@uams.edu.
authors.forename: J
authors.initials: J
authors.lastname: Laudadio
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157, USA. Electronic address: rdagosti@wakehealth.edu.
authors.forename: R B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157, USA; Department of Otolaryngology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: jwaltone@wakehealth.edu.
authors.forename: J D
authors.initials: JD
authors.lastname: Waltonen
authors.affiliation: Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157, USA; Department of Otolaryngology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: csulliva@wakehealth.edu.
authors.forename: C A
authors.initials: CA
authors.lastname: Sullivan
authors.affiliation: Department of Otolaryngology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: rplasser@wakehealth.edu.
authors.forename: R
authors.initials: R
authors.lastname: Rouchard-Plasser
authors.affiliation: Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157, USA. Electronic address: mmatsang@wakehealth.edu.
authors.forename: M
authors.initials: M
authors.lastname: Matsangou
authors.affiliation: Department of Otolaryngology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157, USA. Electronic address: jdbrowne@wakehealth.edu.
authors.forename: J D
authors.initials: JD
authors.lastname: Browne
authors.affiliation: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157, USA. Electronic address: kgreven@wakehealth.edu.
authors.forename: K M
authors.initials: KM
authors.lastname: Greven
authors.affiliation: Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157, USA. Electronic address: mporosni@wakehealth.edu.
authors.forename: M
authors.initials: M
authors.lastname: Porosnicu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000302:isolation & purification*; D000970:Antineoplastic Agents / Q000009:adverse effects; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000209:etiology*; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D010349:Patient Compliance; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies; D012907:Smoking; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Chemotherapy; Human papillomavirus; Oral mucositis; Radiotherapy; Smoking; Squamous cell of head and neck