• 6/30/2008
  • Ann Arbor, MI
  • Francis P. Worden et al.
  • Journal of Clinical Oncology, Vol 26, No 19 (July 1), 2008: pp. 3138-3146

Response and Survival Positively Associated With HPV16 Copy Number

To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response and outcome.

Patients and Methods:
Sixty-six patients (51 male; 15 female) with stage III to IV squamous cell carcinoma of the oropharynx (SCCOP) were treated with one cycle of cisplatin (100 mg/m2) or carboplatin (AUC 6) and with fluorouracil (1,000 mg/m2/d for 5 days) to select candidates for CRT. Those achieving a greater than 50% response at the primary tumor received CRT (70 Gy; 35 fractions with concurrent cisplatin 100 mg/m2 or carboplatin (AUC 6) every 21 days for three cycles). Adjuvant paclitaxel was given to patients who were complete histologic responders. Patients with a response of 50% or less underwent definitive surgery and postoperative radiation. Pretreatment biopsies from 42 patients were tested for high-risk HPV.

Fifty-four of 66 patients (81%) had a greater than 50% response after IC. Of these, 53 (98%) received CRT, and 49 (92%) obtained complete histologic response with a 73.4% (47 of 64) rate of organ preservation. The 4-year overall survival (OS) was 70.4%, and the disease-specific survival (DSS) was 75.8% (median follow-up, 64.1 months). HPV16, found in 27 of 42 (64.3%) biopsies, was associated with younger age (median, 55 v 63 years; P = .016), sex (22 of 30 males [73.3%] and five of 12 females [41.7%]; P = .08), and nonsmoking status (P = .037). HPV titer was significantly associated with IC response (P = .001), CRT response (P = .005), OS (P = .007), and DSS (P = .008).

Although the numbers in this study are small, IC followed by CRT is an effective treatment for SCCOP, especially in patients with HPV-positive tumors; however, for patients who do not respond to treatment, alternative treatments must be developed.

Supported in part by Grants No. R01 DE13346 and P30 DC 05188 from the National Institutes of Health (NIH) NIDCR; Head and Neck Cancer SPORE Grant No. P50 CA97248; Cancer Center Support Grant No. P30 CA46592; and Grants from the state of Michigan.

Francis P. Worden, Bhavna Kumar, Julia S. Lee, Gregory T. Wolf, Kitrina G. Cordell, Jeremy M.G. Taylor, Susan G. Urba, Avraham Eisbruch, Theodoros N. Teknos, Douglas B. Chepeha, Mark E. Prince, Christina I. Tsien, Nisha J. D’Silva, Kun Yang, David M. Kurnit, Heidi L. Mason, Tamara H. Miller, Nancy E. Wallace, Carol R. Bradford, Thomas E. Carey

Authors’ affiliations:
From the Department of Internal Medicine, Division of Hematology-Oncology, Department of Otolaryngology–Head and Neck Surgery, Comprehensive Cancer Center, Department of Periodontics and Oral Medicine, Department of Pathology, Department of Biostatistics, Department of Radiation Oncology; Department of Pediatrics, and Department of Pharmacology, University of Michigan, Ann Arbor, MI

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