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Chemo- and radiotherapy especially effective in HPV-linked oropharyngeal tumors
Response and survival were positively associated with HPV16 copy number.
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Induction chemotherapy as a selection method for concurrent chemoradiotherapy was found to be an effective treatment method for advanced oropharyngeal cancer, and better response to the treatment was associated with the presence of human papilloma virus.
Previous research into the increasing incidence of oral/oropharyngeal tumors has indicated HPV as an etiologic factor. Although some reports suggest that HPV-positive individuals with these tumors have better outcomes, the reports have not been unanimous. Researchers at the University of Michigan Comprehensive Cancer Center in Ann Arbor tested the efficacy of induction chemotherapy followed by concurrent chemoradiotherapy or surgery/radiotherapy and assessed the effect of HPV on response and outcome.
Study design
The study included 66 patients (51 men) with stage III to IV squamous cell carcinoma of the oropharynx. Patients were treated with one cycle of cisplatin (100 mg/m2) or carboplatin (AUC 6) as well as 5-fluorouracil (1,000 mg/m2 per day for five days). This regimen was used as a selection method for those eligible for chemoradiotherapy: patients who achieved a greater than 50% response at the primary tumor received chemoradiotherapy. Patients with a complete histologic response were given adjuvant paclitaxel. Pretreatment biopsies of 42 patients were tested for high-risk HPV.
Fifty-four of the 66 patients (81%) achieved the 50% response rate and 53 of these patients received chemoradiotherapy. Among those 53 patients, 49 (92%) achieved a complete histologic response with a 73.4% rate of organ preservation. The four-year overall survival rate was 70.4% with a disease-specific survival rate of 75.8%. The median time to follow-up was 64 months.
HPV16 was found in 27 of the 42 patients tested (64.3%). It was associated with a younger age (median, 55 years vs. 63 years; P=.016), sex (22 of 30 men vs. five of 12 women; P=.08) and nonsmoking status (P=.037). HPV copy number was found to be significantly associated with patients’ response to induction chemotherapy (P=.003). It also had a positive effect on overall survival (HR=0.81; 95% CI 0.70-0.94) and on disease-free survival (HR=0.77; 95% CI 0.63-0.93).
HPV status and response
Of the 27 HPV-positive patients, 25 were responders to induction chemotherapy and 24 were responders to chemoradiotherapy. Of the 15 HPV-negative patients, 10 responded to induction chemotherapy and seven of those 10 responded to chemoradiotherapy. The positive associations between HPV and response and survival were maintained after adjusting for variables including sex, smoking status, T class, N class, age and primary tumor site.
Francis Worden, MD, an assistant professor of internal medicine at the University of Michigan, said that this research further separates oropharyngeal tumors based on etiology. “The biggest challenge is how best to treat patients with tumors that stem from tobacco and alcohol use as opposed to tumors linked to HPV,” he said in a press release. “We now know they’re two different cancers.” – by Dave Levitan
For more information:
- Worden FP, Kumar B, Lee JS, et al. Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number. J Clin Oncol. 2008;10.1200/JCO.2007.12.7597.