Competing Causes of Death and Medical Comorbidities Among Patients With Human Papillomavirus–Positive vs Human Papillomavirus–Negative Oropharyngeal Carcinoma and Impact on Adherence to Radiotherapy | Chronic Obstructive Pulmonary Disease | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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1.
Gillison  ML, D’Souza  G, Westra  W,  et al.  Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers.  J Natl Cancer Inst. 2008;100(6):407-420.PubMedGoogle ScholarCrossref
2.
Dahlstrom  KR, Little  JA, Zafereo  ME, Lung  M, Wei  Q, Sturgis  EM.  Squamous cell carcinoma of the head and neck in never smoker-never drinkers: a descriptive epidemiologic study.  Head Neck. 2008;30(1):75-84.PubMedGoogle ScholarCrossref
3.
Yung  KC, Piccirillo  JF.  The incidence and impact of comorbidity diagnosed after the onset of head and neck cancer.  Arch Otolaryngol Head Neck Surg. 2008;134(10):1045-1049.PubMedGoogle ScholarCrossref
4.
O’Rorke  MA, Ellison  MV, Murray  LJ, Moran  M, James  J, Anderson  LA.  Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis.  Oral Oncol. 2012;48(12):1191-1201.PubMedGoogle ScholarCrossref
5.
Sartor  MA, Dolinoy  DC, Jones  TR,  et al.  Genome-wide methylation and expression differences in HPV(+) and HPV(-) squamous cell carcinoma cell lines are consistent with divergent mechanisms of carcinogenesis.  Epigenetics. 2011;6(6):777-787.PubMedGoogle ScholarCrossref
6.
Wittekindt  C, Wagner  S, Mayer  CS, Klussmann  JP.  Basics of tumor development and importance of human papilloma virus (HPV) for head and neck cancer.  GMS Curr Top Otorhinolaryngol Head Neck Surg. 2012;11:Doc09.PubMedGoogle Scholar
7.
Klussmann  JP, Weissenborn  SJ, Wieland  U,  et al.  Human papillomavirus-positive tonsillar carcinomas: a different tumor entity?  Med Microbiol Immunol. 2003;192(3):129-132.PubMedGoogle ScholarCrossref
8.
Boscolo-Rizzo  P, Del Mistro  A, Bussu  F,  et al.  New insights into human papillomavirus-associated head and neck squamous cell carcinoma.  Acta Otorhinolaryngol Ital. 2013;33(2):77-87.PubMedGoogle Scholar
9.
Psyrri  A, Sasaki  C, Vassilakopoulou  M, Dimitriadis  G, Rampias  T.  Future directions in research, treatment and prevention of HPV-related squamous cell carcinoma of the head and neck.  Head Neck Pathol. 2012;6(suppl 1):S121-S128.PubMedGoogle ScholarCrossref
10.
Brotherston  DC, Poon  I, Le  T,  et al.  Patient preferences for oropharyngeal cancer treatment de-escalation.  Head Neck. 2013;35(2):151-159.PubMedGoogle ScholarCrossref
11.
Mell  LK, Dignam  JJ, Salama  JK,  et al.  Predictors of competing mortality in advanced head and neck cancer.  J Clin Oncol. 2010;28(1):15-20.PubMedGoogle ScholarCrossref
12.
Rose  BS, Jeong  JH, Nath  SK, Lu  SM, Mell  LK.  Population-based study of competing mortality in head and neck cancer.  J Clin Oncol. 2011;29(26):3503-3509.PubMedGoogle ScholarCrossref
13.
Argiris  A, Brockstein  BE, Haraf  DJ,  et al.  Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemoradiotherapy.  Clin Cancer Res. 2004;10(6):1956-1962.PubMedGoogle ScholarCrossref
14.
Bese  NS, Hendry  J, Jeremic  B.  Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation.  Int J Radiat Oncol Biol Phys. 2007;68(3):654-661.PubMedGoogle ScholarCrossref
15.
Fesinmeyer  MD, Mehta  V, Blough  D, Tock  L, Ramsey  SD.  Effect of radiotherapy interruptions on survival in Medicare enrollees with local and regional head-and-neck cancer.  Int J Radiat Oncol Biol Phys. 2010;78(3):675-681.PubMedGoogle ScholarCrossref
16.
Herrmann  T, Baumann  M.  Prolongation of latency or overall treatment time by unplanned radiation pauses: the clinical importance of compensation [in German].  Strahlenther Onkol. 2005;181(2):65-76.PubMedGoogle ScholarCrossref
17.
Lindberg  RD, Jones  K, Garner  HH, Jose  B, Spanos  WJ  Jr, Bhatnagar  D.  Evaluation of unplanned interruptions in radiotherapy treatment schedules.  Int J Radiat Oncol Biol Phys. 1988;14(4):811-815.PubMedGoogle ScholarCrossref
18.
Wyatt  RM, Beddoe  AH, Dale  RG.  The effects of delays in radiotherapy treatment on tumour control.  Phys Med Biol. 2003;48(2):139-155.PubMedGoogle ScholarCrossref
19.
Ang  KK, Trotti  A, Brown  BW,  et al.  Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer.  Int J Radiat Oncol Biol Phys. 2001;51(3):571-578.PubMedGoogle ScholarCrossref
20.
Byers  RM, Clayman  GL, Guillamondequi  OM, Peters  LJ, Goepfert  H.  Resection of advanced cervical metastasis prior to definitive radiotherapy for primary squamous carcinomas of the upper aerodigestive tract.  Head Neck. 1992;14(2):133-138.PubMedGoogle ScholarCrossref
21.
Garden  AS, Weber  RS, Ang  KK, Morrison  WH, Matre  J, Peters  LJ.  Postoperative radiation therapy for malignant tumors of minor salivary glands: outcome and patterns of failure.  Cancer. 1994;73(10):2563-2569.PubMedGoogle ScholarCrossref
22.
Bourhis  J, Overgaard  J, Audry  H,  et al; MARCH Collaborative Group.  Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.  Lancet. 2006;368(9538):843-854.PubMedGoogle ScholarCrossref
23.
Baujat  B, Bourhis  J, Blanchard  P,  et al; MARCH Collaborative Group.  Hyperfractionated or accelerated radiotherapy for head and neck cancer.  Cochrane Database Syst Rev. 2010;(12):CD002026.PubMedGoogle Scholar
24.
Hendry  JH, Bentzen  SM, Dale  RG,  et al.  A modelled comparison of the effects of using different ways to compensate for missed treatment days in radiotherapy.  Clin Oncol (R Coll Radiol). 1996;8(5):297-307.PubMedGoogle ScholarCrossref
Original Investigation
April 2014

Competing Causes of Death and Medical Comorbidities Among Patients With Human Papillomavirus–Positive vs Human Papillomavirus–Negative Oropharyngeal Carcinoma and Impact on Adherence to Radiotherapy

Author Affiliations
  • 1Department of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento
  • 2Department of Otolaryngology–Head and Neck Surgery, University of California Davis Comprehensive Cancer Center, Sacramento
  • 3Department of Pathology, University of California Davis Comprehensive Cancer Center, Sacramento
  • 4Division of Biostatistics, Department of Public Health Sciences, University of California Davis School of Medicine, Sacramento
JAMA Otolaryngol Head Neck Surg. 2014;140(4):312-316. doi:10.1001/jamaoto.2013.6732
Abstract

Importance  Survival of patients with head and neck cancer can be affected by competing causes of mortality, as well as comorbidities that result in radiation treatment interruptions.

Objective  To discern how differences in preexisting medical and psychosocial comorbidities potentially influence adherence to radiation therapy according to human papillomavirus (HPV) status.

Design, Setting, and Participants  Retrospective analysis at a comprehensive cancer center of 162 consecutive patients with locally advanced squamous cell carcinoma of the oropharynx treated with primary chemoradiation (n = 95) or primary surgery followed by adjuvant radiation (n = 67). Immunostaining for p16 was used to determine HPV status.

Main Outcomes and Measures  Difference in alcohol, tobacco, and marijuana use was compared between patients with HPV-positive and HPV-negative tumors, as well as the prevalence of the following comorbidities: diabetes mellitus, chronic obstructive pulmonary disease (COPD), anxiety disorder, and major depression. The number of total missed treatment days was analyzed as both a continuous and categorical variable.

Results  Rates of self-reported heavy alcohol use (47% vs 16%; P = .02) and any marijuana use (47% vs 23%; P = .003) were significantly higher among HPV-negative patients. Fifty-four percent of HPV-positive patients self-identified as never smokers, compared with only 12% of HPV-negative patients (P < .001). HPV-negative patients had more missed treatment days (mean, 2.8 vs 1.7 days; P = .02), as well as an increased rate of at least 5 missed days (24% vs 10%; P = .04), and higher prevalences of COPD (12% vs 7%; P = .37) and anxiety disorder (12% vs 6%; P = .35).

Conclusions and Relevance  Pronounced differences exist in lifestyle habits between patients with HPV-negative and HPV-positive oropharyngeal cancer at diagnosis. These differences, as well as those of medical and psychosocial burden, may contribute to observed discrepancies in treatment adherence and need to be considered in outcomes reporting and clinical trial design.

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