HUMAN-PAPILLOMAVIRUS GENOTYPE AS A MAJOR DETERMINANT OF THE COURSE OFCERVICAL-CANCER

Purpose: To determine whether the prognosis of invasive cancers of the uterine cervix is related to the type of human papillomavirus (HPV) a ssociated with the tumor. Patients and Methods: Two hundred ninety-sev en patients with invasive cervical cancer were prospectively registere d from 1986 to 1994. HPV typing was performed on DNA extracted from fr ozen tumor specimens by means of Southern blot hybridization (SBH) and polymerase chain reaction (PCR) techniques, The median follow-vp was 38 months. Results: HPV sequences were detected in 246 patients (83%): 150 patients had HPV16, 31 patients held HPV18, and 14 patients had o ne of the intermediate-oncogenic-risk HPV types (HPV31, 33, 35, 52, 58 ). In 51 patients, HPV type remained undetermined, and in 51 patients, no viral sequences were found. No significant associations were obser ved between virologic data and tumor stage or node status. The 5-year disease-free survival (DFS) rate was 100% for patients with intermedia te-risk HPV-associated tumors, 58% for patients with HPV16-positive tu mors, and 38% for patients with HPV18-positive rumors (P = .02). In mu ltivariate analysis, patients with HPV18-associated tumors had a relat ive risk (RR) of death 2.4 times greater (95% confidence interval [CI] , 1.29-4.59) than that for patients with HPV16, and 4.4 times greater (95% CI, 3.48-5.32) than that for patients with a tumor associated wit h a viral type different from HPV16/18. Conclusion: The prognosis for invasive cancers of the uterine cervix is dependent on the oncogenic p otential of the associated HPV type. HPV typing may provide a prognost ic indicator for individual patients and is of potential use in defini ng specific therapies against HPV-harboring tumor cells. J Clin Oncol 16:2613-2619. (C) 1998 by American Society of Clinical Oncology.