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Role of Human Papillomavirus Genotype in Prognosis of Early-Stage Cervical Cancer Undergoing Primary Surgery

Chyong-Huey Lai, Chee-Jen Chang, Huei-Jean Huang, Swei Hsueh, Angel Chao, Jung-Erh Yang, Cheng-Tao Lin, Shang-Lang Huang, Ji-Hong Hong, Hung-Hsueh Chou, Tzu-I Wu, Kuan-Gen Huang, Chun-Chieh Wang, Ting-Chang Chang

From the Departments of Obstetrics and Gynecology, Pathology, and Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine; and Graduate Institutes of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan

Address reprint requests to Chyong-Huey Lai, MD, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, 5 Fu-Shin St, Kueishan, Taoyuan 333, Taiwan; e-mail: sh46erry{at}ms6.hinet.net

Purpose: Our aim was to evaluate the prognostic significance of human papillomavirus (HPV) genotype in early-stage cervical carcinoma primarily treated with surgery in a large tertiary referral medical center.

Patients and Methods: Consecutive patients who underwent primary surgery for invasive cervical carcinoma of International Federation of Gynecology and Obstetrics (FIGO) stage I to IIA between 1993 and 2000 were retrospectively reviewed. Polymerase chain reaction (PCR) using a general primer set followed by reverse-blot detection of 38 types of HPV DNA in a single reaction was performed for genotyping. E6 type-specific PCR was performed to validate multiple types.

Results: A total of 1,067 eligible patients were analyzed. HPV DNA sequences were detected in 95.1% of the specimens, among which 9.6% contained multiple types. HPV 16 was detected in 63.8% of the samples, and HPV 18 was detected in 16.5% of the samples. The median follow-up time of surviving patients was 77 months. By multivariate analysis, FIGO stage, lymph node metastasis, depth of cervical stromal invasion, grade of differentiation, and HPV 18 positivity were significantly related to cancer relapse. FIGO stage II, deep stromal invasion, parametrial extension, HPV 18 positivity, and age older than 45 years were significant predictors for death. Using the seven selected variables from either recurrence-free or overall survival analysis, death-predicting (P < .0001) and relapse-predicting (P < .0001) models classifying three risk groups (low, intermediate, and high risk) were constructed and endorsed by internal validation.

Conclusion: The independent prognostic value of HPV genotype is confirmed in this study. The prognostic models could be useful in counseling patients and stratifying patients in future clinical trials.

Supported by Grants No. NSC93-2314-B-182-036 and NSC94-2314-B-182-011 from the National Science Council–Taiwan.

Presented in part at the 38th Annual Meeting on Women's Cancer, March 3-7, 2007, San Diego, CA.

C.-H.L., C.-J.C., and H.-J.H. contributed equally to this work.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.