Impact of human papillomavirus genotype on response to treatment and survival in patients receiving radiotherapy for squamous cell carcinoma of the cervix

Ferdousi,Jannatul; Nagai,Yutaka; Asato,Tsuyoshi; Hirakawa,Makoto; Inamine,Morihiko; Kudaka,Wataru; Kariya,Ken-ichi; Aoki,Yoichi

doi:10.3892/etm_00000083

Impact of human papillomavirus genotype on response to treatment and survival in patients receiving radiotherapy for squamous cell carcinoma of the cervix

Authors:
- Jannatul Ferdousi
- Yutaka Nagai
- Tsuyoshi Asato
- Makoto Hirakawa
- Morihiko Inamine
- Wataru Kudaka
- Ken-ichi Kariya
- Yoichi Aoki
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
Published online on: May 1, 2010 https://doi.org/10.3892/etm_00000083
Pages: 525-530

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

To determine the clinical implications and prognostic value of the human papillomavirus (HPV) genotype, we evaluated the various HPV types in patients receiving radiotherapy for squamous cell carcinoma of the cervix. The study population included 113 invasive squamous cell carcinoma patients treated with radiation or chemoradiation between 1993 and 2002. The median age of the patients was 61 years. Tumors were classi?ed by the International Federation of Gynecology and Obstetrics staging as stage IB in 11 patients, stage II in 39, stage III in 57 and stage IVA in 6 patients. To investigate HPV infection and its genotypes in the tumor specimens, L1 consensus PCR was performed followed by the direct nucleotide sequencing of the PCR products. Ninety-five samples (84.1%) were positive for HPV DNA. The most prevalent type was HPV-16 (34.7%). Poorer response to radiotherapy was observed in the patients with the HPV-16 genotype, in which 7 of the 33 patients had persistent disease. Only 1 of the 10 patients with HPV-58, 1 of the 5 with HPV-31 and 5 of the 10 patients with HPV-33 had a recurrence. The 5-year survival rate was 90, 80, 69.4 and 39% in the HPV-58, HPV-31, HPV-16 and HPV-33 type groups, respectively. Patients with HPV-31 and HPV-58 types were found to have better survival, whereas patients with the HPV-33 type experienced a higher risk of death. HPV genotyping may serve as a potential biomarker of response to radiation and prognosis in cervical carcinoma patients undergoing radio- or chemoradiotherapy.

View Figures

View References

1.	Bosch FX, Manos MM, Munoz N, et al: Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International Biological Study on Cervical Cancer (IBSCC) Study Group. J Natl Cancer Inst. 87:796–802. 1995. View Article : Google Scholar
2.	Liaw KL, Glass AG, Manos MM, et al: Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions. J Natl Cancer Inst. 91:954–960. 1999. View Article : Google Scholar : PubMed/NCBI
3.	Walboomers JM, Jacobs MV, Manos MM, et al: Human papillomavirus is a necessary cause of invasive cancer worldwide. J Pathol. 189:12–19. 1999. View Article : Google Scholar
4.	Kosary CL: FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: an analysis of 1973–87 SEER cases of cancers of the endometrium, cervix, ovary, vulva and vagina. Semin Surg Oncol. 10:31–46. 1994.PubMed/NCBI
5.	Coia L, Won M, Lanciano R, et al: The patterns of care outcome study for cancer of the uterine cervix. Results of the Second National Practice Survey Cancer. 66:2451–2456. 1990.PubMed/NCBI
6.	Schwartz SM, Daling JR, Shera KA, et al: Human papillomavirus and prognosis of invasive cervical cancer: a population-based study. J Clin Oncol. 19:1906–1915. 2001.PubMed/NCBI
7.	Bachtiary B, Obermair A, Dreier B, et al: Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer. Int J Cancer. 102:237–243. 2002. View Article : Google Scholar : PubMed/NCBI
8.	Kristensen GB, Karlsen F, Jenkins A, et al: Human papilloma virus has no prognostic significance in cervical carcinoma. Eur J Cancer. 32A:1349–1353. 1996. View Article : Google Scholar : PubMed/NCBI
9.	Van Bommel PF, van den Brule AJ, Helmerhorst TJ, et al: HPV DNA presence and HPV genotypes as prognostic factors in low-stage squamous cell cervical cancer. Gynecol Oncol. 48:333–337. 1993.PubMed/NCBI
10.	Lai HC, Sun CA, Yu MH, et al: Favorable clinical outcome of cervical cancers infected with human papilloma virus type 58 and related types. Int J Cancer. 84:553–557. 1999. View Article : Google Scholar : PubMed/NCBI
11.	Huang LW, Chao SL and Hwang JL: Human papillomavirus-31-related types predict better survival in cervical carcinoma. Cancer. 100:327–334. 2004. View Article : Google Scholar : PubMed/NCBI
12.	Graflund M, Sorbe B, Sigurdardottir S, et al: HPV-DNA, vascular space invasion, and their impact on the clinical outcome in early-stage cervical carcinomas. Int J Gynecol Cancer. 14:896–902. 2004. View Article : Google Scholar : PubMed/NCBI
13.	Tong SY, Lee YS, Park JS, et al: Papillomavirus genotype as a prognostic factor in carcinoma of the uterine cervix. Int J Gynecol Cancer. 17:1307–1313. 2007. View Article : Google Scholar : PubMed/NCBI
14.	Hirakawa M, Nagai Y, Inamine M, et al: Predictive factors of distant recurrence in locally advanced squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy. Gynecol Oncol. 108:126–129. 2008. View Article : Google Scholar : PubMed/NCBI
15.	Yoshikawa H, Kawana T, Kitagawa K, et al: Detection and typing of multiple genital human papillomaviruses by DNA amplification with consensus primers. Jpn J Cancer Res. 82:524–531. 1991. View Article : Google Scholar : PubMed/NCBI
16.	Asato T, Maehama T, Nagai Y, et al: A large case-control study on cervical cancer risk of HPV infection in Japan by nucleotide sequencing-based genotyping. J Infect Dis. 189:1829–1832. 2004. View Article : Google Scholar : PubMed/NCBI
17.	Inoue M, Sakaguchi J, Sasagawa T, et al: The evaluation of human papillomavirus DNA testing in primary screening for cervical lesions in a large Japanese population. Int J Gynecol Cancer. 16:1007–1013. 2006. View Article : Google Scholar : PubMed/NCBI
18.	Miura S, Matsumoto K, Oki A, et al: Do we need a different strategy for HPV screening and vaccination in East Asia? Int J Cancer. 119:2713–2715. 2006. View Article : Google Scholar : PubMed/NCBI
19.	Hagmar B, Christensen JJ, Johansson B, et al: Implications of human papillomavirus type for survival in cervical squamous cell carcinoma. Int J Gynecol Cancer. 5:341–345. 1995. View Article : Google Scholar : PubMed/NCBI
20.	Barbosa MS and Schlegel R: The E6 and E7 genes of HPV-18 are sufficient for inducing two-stage in vitro transformation of human keratinocytes. Oncogene. 4:1529–1532. 1989.PubMed/NCBI