Originally published as JCO Early Release 10.1200/JCO.2009.22.4659 on September 21 2009

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Low Initial Human Papilloma Viral Load Implicates Worse Prognosis in Patients With Uterine Cervical Cancer Treated With Radiotherapy

From the Research Institute and Hospital, National Cancer Center; Department of Obstetrics and Gynecology, Dongguk University Ilsan Hospital, College of Medicine, Goyang, Gyeonggi; and Department of Radiation Oncology, Hallym University Kangdong Sacred Heart Hospital, Anyang, Korea.

Corresponding author: Joo-Young Kim, MD, PhD, Research Institute and Hospital, National Cancer Center, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi 410-769, Korea; e-mail: jooyoungcasa{at}ncc.re.kr.

Purpose To evaluate whether human papillomavirus (HPV) viral load measured in cervical smear and HPV type 18 are associated with radiotherapy outcomes in uterine cervical cancer.

Patients and Methods HPV DNA was semiquantitatively measured in the cervical smears of 169 radiotherapy patients. HPV viral load was classified as low or high according to median HPV DNA titer and examined for its prognostic value. The multivariable Cox proportional hazards model was used to adjust for covariates. A relapse-predicting model was constructed to classify three risk groups for disease-free survival (DFS), which were used for internal validation.

Results Patients with lower HPV viral load showed worse DFS in univariate analysis. HPV type 18, younger patient age, stage group, nodal status, histologic grade, and histologic type were other prognostic factors for poor DFS. Among these factors, all except stage group were associated with HPV viral load. Multivariate analysis showed the strong influence of HPV viral load for poor DFS. The prognostic model developed using our outcome data performed well in predicting the risk of relapse.

Conclusion Our data suggest that HPV viral load is a strong independent prognostic factor for DFS. HPV type 18 showed a significant relationship with poor radiotherapy outcome in univariate analysis, but not in multivariate analysis.

Supported by Grant No. 0810270 from the National Cancer Center, Goyang, Korea, and conducted under Research Agreement E33024 (Optimizing Treatment of Cervix Cancer Using Radiotherapy and Analysis of Virally-Associated Cellular Resistance) from the International Atomic Energy Agency, Vienna, Austria.

Presented in part as a poster at the 24th International Papillomavirus Conference and Clinical Workshop, November 3-9, 2007, Beijing, China.

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

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