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Human Papillomavirus and Prognosis of Invasive Cervical Cancer: A Population-Based Study

From the Programs in Biostatistics and Epidemiology, Division of Public Health Sciences, and Program in Cancer Biology, Division of Human Biology, Fred Hutchinson Cancer Research Center; and Departments of Biostatistics and Epidemiology, School of Public Health and Community Medicine, and Departments of Microbiology and Pathology, School of Medicine, University of Washington, Seattle, Washington.

Address reprint requests to Stephen M. Schwartz, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N (MP-381), PO Box 19024, Seattle, WA 98109-1024.

PURPOSE: To determine the association between human papillomavirus (HPV) type and prognosis of patients with invasive cervical carcinoma.

PATIENTS AND METHODS: Patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IV cervical cancer between 1986 and 1997 while residents of three Washington State counties were included (n = 399). HPV typing was performed on paraffin-embedded tumor tissue using polymerase chain reaction methods. Patients were observed for a median of 50.8 months. Total mortality (TM) and cervical cancer–specific mortality (CCSM) were determined. Hazards ratios (HR) adjusted for age, stage, and histologic type were estimated using multivariable models.

RESULTS: Eighty-six patients had HPV 18–related tumors and 210 patients had HPV 16–related tumors. Cumulative TM among patients with HPV 18–related tumors and among patients with HPV 16–related tumors were 33.7% and 27.6%, respectively; cumulative CCSM in these two groups were 26.7% and 18.1%, respectively. Compared with patients with HPV 16–related cancers, patients with HPV 18–related cancers were at increased risk for TM (HR_TM, 2.2; 95% confidence interval [CI], 1.3 to 3.6) and CCSM (HR_CCSM, 2.5; 95% CI, 1.4 to 4.4). The HPV18 associations were strongest for patients with FIGO stage IB or IIA disease (HR_TM, 3.1; 95% CI, 2.3 to 4.2; and HR_CCSM, 5.8; 95% CI, 3.9 to 8.7), whereas no associations were observed among patients with FIGO stage IIB to IV disease. Virtually identical associations were found in the subset of patients with squamous cell carcinoma (n = 219).

CONCLUSION: HPV 18–related cervical carcinomas, particularly those diagnosed at an early stage, are associated with a poor prognosis. Elucidating the mechanism or mechanisms underlying this association could lead to new treatment approaches for patients with invasive cervical carcinoma.

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