Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer

International Journal of Cancer - Tập 102 Số 3 - Trang 237-243 - 2002
Barbara Bachtiary1, Andreas Obermair2,3, Bettina Dreier1, Peter Birner4, G. Breitenecker4, Tomas‐Hendrik Knocke1, Edgar Selzer5,1, Richard Pötter1
1Department of Radiotherapy and Radiobiology, University Hospital Vienna, Vienna, Austria
2Department of Gynecology and Obstetrics, University Hospital Vienna, Vienna, Austria
3Queensland Center for Gynecological Cancer, Royal Women's Hospital, Brisbane, Australia
4Clinical Institute of Pathology, University Hospital Vienna, Vienna, Austria
5Center of Excellence for Clinical and Experimental Oncology (CLEXO), University Hospital Vienna, Vienna, Austria

Tóm tắt

AbstractTo obtain information on the incidence and the clinical significance of infection with various types of the human papillomavirus (HPV) in cancer of the uterine cervix, we retrospectively examined the HPV status of 106 patients who had received radical radiotherapy for cervical cancer stages IB to IIIB. DNA was extracted from formalin‐fixed, paraffin‐embedded biopsies and PCR was carried out to identify HPV types 16, 18, 31, 35, 33 and 45. To detect additional HPV types, consensus PCR products were cloned and sequenced. A catalyzed signal‐amplified colorimetric in situ hybridization was carried out in 84 of 106 specimens as a positive control. Response to therapy, progression‐free survival (PFS) and cervical cancer‐specific survival (CCSS) were the statistical endpoints. Survival analysis was carried out using univariate and multivariate analysis (Cox regression). Ninety‐six patients (90.6%) were HPV‐positive and 42/96 (43.7%) were positive for multiple HPV types. Eight patients had persistent disease after radiotherapy. From these 8 patients, 7 were infected with multiple HPV types and only 1 patient had an infection with a single HPV type. After a median follow up period of 50 months, patients with multiple HPV infection had a significantly shorter PFS and CCSS compared to those with single HPV infection (24.8% and 34.9% vs. 64% and 60.8%, Log rank, p < 0.01 and 0.04). In multivariate analysis, the presence of multiple HPV types (RR 1.9), node status (RR 2.3), tumor size (RR 3.2) and histologic type (RR 4.8) were independent prognostic factors of CCSS. Our results demonstrate that the presence of multiple HPV types is associated with poor response and with reduced survival in cervical cancer patients who receive radiotherapy as the primary treatment. © 2002 Wiley‐Liss, Inc.

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Tài liệu tham khảo

Ferlay J, 2001, GLOBOCAN 2000: cancer incidence, mortality and prevalence worldwide, version 1.0

10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F

10.1093/jnci/87.11.796

10.1016/S1386-6532(00)00125-6

10.1016/0002-9378(95)90633-9

10.1002/(SICI)1097-0142(19961101)78:9<1935::AID-CNCR14>3.0.CO;2-Z

10.1200/JCO.1998.16.8.2613

10.1200/JCO.2001.19.7.1906

10.1016/0140-6736(90)92693-C

10.1016/0140-6736(91)91773-N

DeBritton RC, 1993, Human papillomaviruses and other influences on survival from cervical cancer in Panama, Obstet Gynecol, 81, 19

10.1002/1097-0142(19890301)63:5<897::AID-CNCR2820630517>3.0.CO;2-W

10.1016/0090-8258(92)90233-9

10.1006/gyno.1993.1058

10.1200/JCO.1997.15.2.610

10.1016/0959-8049(96)00089-5

10.1002/(SICI)1097-0142(19990501)85:9<2011::AID-CNCR19>3.0.CO;2-N

10.1096/fj.00-0728fje

10.1002/(SICI)1097-0215(20000215)85:4<486::AID-IJC7>3.0.CO;2-S

Sasagawa T, 2001, High‐risk and multiple human papillomavirus infections associated with cervical abnormalities in Japanese women, Cancer Epidemiol Biomarkers Prev, 10, 45

10.1099/00222615-46-1-54

10.1016/S1286-4579(00)00276-8

10.1002/(SICI)1097-0215(19980209)75:4<546::AID-IJC9>3.0.CO;2-T

10.1093/jnci/92.6.464

10.1002/jmv.1085

10.1056/NEJM199802123380703

10.1016/S0140-6736(98)12490-X

10.1016/S1278-3218(00)88900-3

10.1126/science.2448875

10.1099/0022-1317-76-4-1057

10.1128/jcm.34.9.2095-2100.1996

10.1038/modpathol.3880375

10.1002/(SICI)1097-0215(19991222)84:6<553::AID-IJC2>3.0.CO;2-4

10.1002/path.855

10.1128/JCM.34.3.745-747.1996

10.1128/JCM.37.8.2508-2517.1999

10.1016/0092-8674(93)90384-3

10.1073/pnas.89.16.7491

Tsang NM, 1995, Abrogation of p53 function by transfection of HPV16 E6 gene enhances the resistance of human diploid fibroblasts to ionizing radiation, Oncogene, 10, 2403

10.1073/pnas.95.5.2290

10.1002/1097-0142(20010101)91:1<80::AID-CNCR11>3.0.CO;2-E

10.1093/jnci/91.3.226

10.1086/323081

10.1086/317638