Treatment response in the neck: p16+ versus p16− oropharyngeal cancer

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Abstract

To compare nodal response rates following chemoradiotherapy in patients with p16+ and p16- oropharyngeal squamous cell carcinoma (OPSCC).

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Most cited references 13

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Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial.

Danny Rischin, Richard J Young, Richard Fisher … (2010)

To determine the prognostic importance of p16 and human papillomavirus (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial. Patients with stage III or IV head and neck squamous cell cancer were randomly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine. In this substudy, analyses were restricted to patients with oropharyngeal cancer. p16 was detected by immunohistochemistry, and HPV was detected by in situ hybridization and polymerase chain reaction. Slides were available for p16 assay in 206 of 465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172 patients. One hundred six (57%) of 185 were p16-positive, and in patients evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also HPV-positive. Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group (ECOG) performance status. p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74; P = .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P = .003). p16 was a significant prognostic factor on multivariable analysis (HR, 0.45; 95% CI, 0.21 to 0.96; P = .04). p16-positive patients had lower rates of locoregional failure and deaths due to other causes. There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients (HR, 0.33; 95% CI, 0.09 to 1.24; P = .13). HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.

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Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity.

Maura L. Gillison (2004)

There is currently sufficient evidence to conclude that human papillomavirus (HPV) plays a role in the pathogenesis of a distinct subset of head and neck squamous cell cancers (HNSCC), particularly tonsillar cancers. There is a strong and consistent association between high-risk HPV types, specifically HPV16, a known human carcinogen, and these distinctive oropharyngeal cancers with molecular characteristics indicative of viral oncogene function. Risk for HPV-HNSCC is increased by certain sexual behaviors after consideration of alcohol and tobacco exposure, consistent with an extensive literature that has established HPV infection as a sexually transmitted disease. Furthermore, exposure to HPV16 has been associated with increased risk for subsequent development of oropharyngeal cancer. Prophylactic and therapeutic vaccines targeted against the viral capsid components and oncoproteins will provide the ultimate evidence for a role for HPV in HNSCC, if demonstrated to be effective in the prevention or therapy of this disease. It is time for clinician scientists to translate knowledge of this newly recognized disease entity into potential applications for the prevention, detection, and treatment of HPV-HNSCC.

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Tirapazamine, Cisplatin, and Radiation versus Fluorouracil, Cisplatin, and Radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02).

David Lamb, Michael Poulsen, June Corry … (2005)

To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial. One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost). Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms. Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.