NEW YORK (Reuters Health) Jun 04 - A high titer of high-risk HPV (human papillomavirus) and low expression of epidermal growth factor receptor (EGFR) are markers of good response to organ-sparing therapy for advanced squamous cell carcinoma of the oropharynx, according to a research team at the University of Michigan in Ann Arbor.

In contrast, high EGFR expression, low p53 combined with high Bcl-xL expression, female sex, and smoking are associated with poor treatment outcome, they report in the July 1 issue of the Journal of Clinical Oncology, available online May 12.

"The chemotherapy and radiation therapy we use to treat this type of cancer is very aggressive," senior author Dr. Thomas Carey notes in a press statement. "If we can identify those patients most likely to respond, we could reduce the intensity of the therapy for those likely to have the best outcomes."

In a prospective study, Dr. Carey's group examined pretreatment biopsies from 50 patients with stage III-IV squamous cell carcinoma of the oropharynx. They measured HPV loads, EGFR expression, and levels of the tumor suppressor p53, the antiapoptotic protein Bcl-xL, and p16, a kinase inhibitor that blocks cell cycle progression.

Induction chemotherapy comprised one cycle of cisplatin or carboplatin for 1 day and fluorouracil for 5 days. The 42 patients who exhibited a > 50% response at the primary site were treated with combined chemotherapy and radiation therapy.

None of the nonresponders survived despite surgery and radiation treatment. Thirty of 38 patients who responded to chemo/radiotherapy survived to the end of the study.

"In our cohort, EGFR, HPV16, and p16 each independently predicted survival and, as combined markers, identified the patients with the best and worst survival," the authors report. The worst outcomes were observed in patients who were current smokers with high tumor EGFR expression.

"Pretreatment biopsies to identify those nonsmoking patients with high HPV loads and low EGFR expression for the least aggressive therapy" would minimize treatment morbidity, Dr. Carey and his associates conclude.

They also recommend smoking cessation, and suggest that, where appropriate, EGFR blockade and cell survival protein inhibitors may improve survival.

J Clin Oncol 2008;26.