Response to Therapy and Outcomes in Oropharyngeal Cancer Are Associated With Biomarkers Including Human Papillomavirus, Epidermal Growth Factor Receptor, Gender, and Smoking

Abstract

IntroductionAppropriate treatment of advanced oral/oropharyngeal squamous cell carcinoma is a difficult challenge. Less than 50% of patients survive more than 5 years 1 . Surgery affects visible structures important for eating, swallowing, speaking, and human interaction. Organ sparing treatments can save important structures and can lead to improved outcome in patients who respond to such therapy. Induction chemotherapy followed by concurrent chemoradiation has shown efficacy both for organ sparing and survival in laryngeal cancer with 3 yr survival rates of 86% 1, 2 . For oral cancer and oropharyngeal cancer this treatment is less effective with 3 yr survival rates of 47% and 67% respectively 3 .Corresponding Author: Dr. Carey, 1301 East Ann St., Ann Arbor, MI 48109-0506. Conflict of Interest: Dr. Kurnit has interest in a company (SensiGen LLC) that is developing the HPV detection method.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Thus, it is important to understand the factors that determine which tumors respond well and which tumors fail to respond so that new targeted therapeutic approaches can be developed to overcome resistance and improve outcome. We have previously demonstrated that p53 status and BclxL are important determinants of response to cisplatin in HNSCC in vitro 4 . Furthermore, high and low Bcl-xL expression in pretreatment tumor biopsies containing wild type p53 identifies those oropharynx cancer patients with the worst and best survival respectively. In this report, we extend our analysis of predictive markers in oropharynx cancer. NIH Public AccessCarcinoma of the head and neck is the 6 th most common malignancy worldwide. Smoking remains the number one risk factor for head and neck cancer and may also influence response to therapy. Despite declining smoking rates in the United States, incidence of oropharyngeal and oral cavity tumors is increasing in young adults. HPV-16 infection is associated with a significant proportion of squamous cell carcinomas of the oropharynx particularly for those lacking other risk factors 5-8 . Epidermal growth factor receptor is overexpressed in up to 90% of HNSCC. High expression of EGFR has been linked to local recurrence after radiation in HNSCC 9 . The purpose of this study was to determine if HPV, EGFR, and smoking are determinants of outcome in patients with advanced oropharyngeal cancer treated on an organ sparing protocol. MethodsPretreatment biopsies were used to prospectively assess predictive biomarkers. A quantitative method that combines PCR and mass spectroscopy to identify HPV type and copy number 1...

A Review of Literature Pertaining to Head and Neck Squamous Cell Carcinoma with Emphasis on the Role of the Human Papilloma Virus

“…A further paper which supports these findings is that of Fakhry [8]. After adjustment for age, tumour stage, and ECOG performance status, tumour HPV status was also statistically significantly associated with progression free survival (Figure 4).…”

“…Data on molecular diagnostic tests was derived from general papers on the subject [5] and then specific papers on HPV detection. Certain conclusions in this dissertation were derived from constructing publications, particularly those by Kloazar [6], Kumar [7], Fakhry [8] and Weinberger [9].…”

Staying a Step Ahead of Cancer

“…In the last several years, the association between human papilloma virus (HPV) and head and neck cancer has been solidified (Wansom et al 2010, Albers et al 2005, Sirianni et al 2004, Sirianni, Wang and Ferris 2005, Kumar et al 2007, Kumar et al 2008, Sisk et al 2002. Interestingly, HPV associated head and neck cancers exhibit better prognosis and appear to respond better to chemo-radiation.…”

Human Papillomavirus Infection and Prognostic Predictors in Patients with Oropharyngeal Squamous Cell Carcinoma

“…HR-HPV infection is an independent prognostic indicator (Weinberger et al, 2006;Kumar et al, 2007;Fakhry et al, 2008;Gillison et al, 2000;Hafkamp Kuo et al, 2008;Worden et al, 2008;Lill et al, 2011;Posner et al, 2011). Kuo and colleagues reported that the 5-year overall survival rate of patients with HR-HPV positive OSCC was 89%, which was significantly higher than HR-HPV negative patients (61%, p=0.001) (Kuo et al, 2008).…”