Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer
Open accessAbstract
To 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.
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Bachtiary et al., in a study of 106 cervical cancer patients receiving radiation therapy, found that multiple-type HPV was an independent poor prognostic factor.
“Bachtiary et al. [38], in a study of 106 cervical cancer patients receiving radiation therapy, found that multiple-type HPV was an independent poor prognostic factor.”
From HPV Genotypes distribution in Indian women with and without cervical carcinoma: Implication for HPV vaccination program in Odisha, Eastern India (2017) · cites this paper as [38]
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Research works printed but not linked: 43
- Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2000: cancer incidence, mortality and prevalence worldwide, version 1.0. IARC CancerBase No. 5. Lyon: IARC Press, 2001.
- Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillo- mavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12-9.
- Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) study group. J Natl Cancer Inst 1995;87:796 -802.
- Munoz N. Human papillomavirus and cancer: the epidemiological evidence. J Clin Virol 2000;19:1-5.
- Rose BR, Thomson CH, Simpson JM, Jarrett CS, Elliott PM, Tatter- sall MH, Dalrymple C, Cossart YE. Human papillomavirus deoxyri- bonucleic acid as a prognostic indicator in early-stage cervical cancer: a possible role for type 18. Am J Obstet Gynecol 1995;173:1461-8.
- Nakagawa S, Yoshikawa H, Onda T, Kawana T, Iwamoto A, Taketani Y. Type of human papillomavirus is related to clinical features of cervical carcinoma. Cancer 1996;78:1935-41.
- Lombard I, Vincent-Salomon A, Validire P, Zafrani B, de la Roch- efordiere A, Clough K, Favre M, Pouillart P, Sastre-Garau X. Human papillomavirus genotype as a major determinant of the course of cervical cancer. J Clin Oncol 1998;16:2613-9.
- Schwartz SM, Daling JR, Shera KA, Madeleine MM, McKnight B, Galloway DA, Porter PL, McDougall JK. Human papillomavirus and prognosis of invasive cervical cancer: a population-based study. J Clin Oncol 2001;19:1906 -15.
- Riou G, Favre M, Jeannel D, Bourhis J, Bourhis J, Le Doussal V, Orth G. Association between poor prognosis in early-stage invasive cervi- cal carcinomas and non-detection of HPV DNA. Lancet 1990;335: 1171-4.
- Higgins GD, Davy M, Roder D, Uzelin DM, Phillips GE, Burrell CJ. Increased age and mortality associated with cervical carcinomas negative for human papillomavirus RNA. Lancet 1991;338:910 -31.
- DeBritton RC, Hildesheim A, De Lao SL, Brinton LA, Sathya P, Reeves WC. Human papillomaviruses and other influences on sur- vival from cervical cancer in Panama. Obstet Gynecol 1993;81:19 - 24.
- King LA, Tase T, Twiggs LB, Okagaki T, Savage JE, Adcock LL, Prem KA, Carson LF. Prognostic significance of the presence of human papillomavirus DNA in patients with invasive carcinoma of the cervix. Cancer 1989;63:897-900.
- Jarrell MA, Heintz N, Howard P, Collins C, Badger G, Belinson J, Nason F. Squamous cell carcinoma of the cervix: HPV 16 and DNA ploidy as predictors of survival. Gynecol Oncol 1992;46:361-6.
- van Bommel PF, van den Brule AJ, Helmerhorst TJ, Gallee MP, Gaarenstroom KN, Walboomers JM, Meijer CJ, Kenemans P. HPV DNA presence and HPV genotypes as prognostic factors in low-stage squamous cell cervical cancer. Gynecol Oncol 1993;48:333-7.
- Viladiu P, Bosch FX, Castellsague X, Escriba JM, Hamsikova E, Hofmannova V, Guerrero E, Izquierdo A, Navarro C, Moreo P, Izarzugaza I, Ascunce N, et al. Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2 and E7 peptides as predictors of survival in patients with squamous cell cervical cancer. J Clin Oncol 1997;15:610 -9.
- van Muyden RC, ter Harmsel BW, Smedts FM, Hermans J, Kuijpers JC, Raikhlin NT, Petrov S, Lebedev A, Ramaekers FC, Trimbos JB, Kleter B, Quint WG. Detection and typing of human papillomavirus in cervical carcinomas in Russian women: a prognostic study. Cancer 1999;85:2011-6.
- Hampson L, El Hady ES, Moore JV, Kitchener H, Hampson IN. The HPV16 E6 and E7 proteins and the radiation resistance of cervical carcinoma. FASEB J 2001;15:1445-7.
- Rolon PA, Smith JS, Munoz N, Klug SJ, Herrero R, Bosch X, Llamosas F, Meijer CJ, Walboomers JM. Human papillomavirus infection and invasive cervical cancer in Paraguay. Int J Cancer 2000;85:486 -91.
- Sasagawa T, Basha W, Yamazaki H, Inoue M. High-risk and multiple human papillomavirus infections associated with cervical abnormali- ties in Japanese women. Cancer Epidemiol Biomarkers Prev 2001;10: 45-52.
- Chang DY, Chen RJ, Lee SC, Huang SC. Prevalence of single and multiple infection with human papillomaviruses in various grades of cervical neoplasia. J Med Microbiol 1997;46:54 -60.
- Sebbelov AM, Davidson M, Kruger Kjaer S, Jensen H, Gregoire L, Hawkins I, Parkinson AJ, Norrild B. Comparison of human papillo- mavirus genotypes in archival cervical cancer specimens from Alaska natives, Greenland natives and Danish Caucasians. Microbes Infect 2000;2:121-6.
- Chaouki N, Bosch FX, Munoz N, Meijer CJ, El Gueddari B, El Ghazi A, Deacon J, Castellsague X, Walboomers JM. The viral origin of cervical cancer in Rabat, Morocco. Int J Cancer 1998;75:546 -54.
- Herrero R, Hildesheim A, Bratti C, Sherman ME, Hutchinson M, Morales J, Balmaceda I, Greenberg MD, Alfaro M, Burk RD, Wacholder S, Plummer M, et al. Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica. J Natl Cancer Inst 2000;92:464 -74.
- Fife KH, Cramer HM, Schroeder JM, Brown DR. Detection of mul- tiple human papillomavirus types in the lower genital tract correlates with cervical dysplasia. J Med Virol 2001;64:550 -9.
- Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998;338:423-8.
- Nobbenhuis MAE, Walboomers JMM, Helmerhorst TJM, Rozendaal L, Remmink AJ, Risse EK, van der Linden HC, Voorhorst FJ, Kenemans P, Meijer CJ. Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study. Lancet 1999;345:20 -5.
- Potter R, Knocke TH, Fellner C, Baldass M, Reinthaller A, Kucera H. Definitive radiotherapy based on HDR brachytherapy with iridium 192 in uterine cervix carcinoma: report on the Vienna University Hospital findings (1993-1997) compared to the preceding period in the context of ICRU 38 recommendations. Cancer Radiother 2000;4: 159 -72.
- Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988;239:487- 91.
- de Roda Husman AM, Walboomers JM, van den Brule AJ, Meijer CJ, Snijders PJ. The use of general primers GP5 and GP6 elongated at their 3Ј ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 1995;76:1057- 62.
- Karlsen F, Kalantari M, Jenkins A, Pettersen E, Kristensen G, Holm R, Johansson B, Hagmar B. Use of multiple PCR primer sets for optimal detection of human papillomavirus. J Clin Microbiol 1996; 34:2095-100.
- Birner P, Bachtiary B, Dreier B, Schindl M, Joura EA, Breitenecker G, Oberhuber G. Signal-amplified colorimetric in situ hybridization for assessment of human papillomavirus infection in cervical lesions. Mod Pathol 2001;14:702-9.
- Lai HC, Sun CA, Yu MH, Chen HJ, Liu HS, Chu TY. Favorable clinical outcome of cervical cancers infected with human papilloma virus type 58 and related types. Int J Cancer 1999;84:553-7.
- Quint WG, Scholte G, van Doorn LJ, Kleter B, Smits PH, Lindeman J. Comparative analysis of human papillomavirus infections in cervi- cal scrapes and biopsy specimens by general SPF (10) PCR and HPV genotyping. J Pathol 2001;194:51-8.
- Baay MF, Quint WG, Koudstaal J, Hollema H, Duk JM, Burger MP, Stolz E, Herbrink P. Comprehensive study of several general and type-specific primer pairs for detection of human papillomavirus DNA by PCR in paraffin-embedded cervical carcinomas. J Clin Mi- crobiol 1996;34:745-7.
- Kleter B, van Doorn LJ, Schrauwen L, Molijn A, Sastrowijoto S, ter Schegget J, Lindeman J, ter Harmsel B, Burger M, Quint W. Devel- opment and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus. J Clin Microbiol 1999;37:2508 -17.
- Scheffner M, Huibregtse JM, Vierstra RD, Howley PM. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 1993;75:495-505.
- Kuerbitz SJ, Plunkett BS, Walsh WV, Kastan MB. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci USA 1992;89:7491-5.
- Tsang NM, Nagasawa H, Li C, Little JB. Abrogation of p53 function by transfection of HPV16 E6 gene enhances the resistance of human diploid fibroblasts to ionizing radiation. Oncogene 1995;10:2403-8.
- Song S, Gulliver GA, Lambert P. Human papillomavirus type 16 E6 and E7 oncogenes abrogate radiation-induced DNA damage responses in vivo through p53-dependent and p53-independent pathways. Proc Natl Acad Sci USA 1998;95:2290 -5.
- Ishikawa H, Mitsuhashi N, Sakurai H, Maebayashi K, Niibe H. The effects of p53 status and human papillomavirus infection on the clinical outcome of patients with Stage IIIB cervical carcinoma treated with radiation therapy alone. Cancer 2001;91:80 -9.
- Palefsky JM, Minkoff H, Kalish LA, Levine A, Sacks HS, Garcia P, Young M, Melnick S, Miotti P, Burk R. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)- positive and high-risk HIV-negative women. J Natl Cancer Inst 1999; 91:226 -36.
- Ahdieh L, Klein RS, Burk R, Cu-Uvin S, Schuman P, Duerr A, Safaeian M, Astemborski J, Daniel R, Shah K. Prevalence, incidence, and type-specific persistence of human papillomavirus in human immunodeficiency virus (HIV)-positive and HIV-negative women. J Infect Dis 2001;184:682-90.
- Liaw KL, Hildesheim A, Burk RD, Gravitt P, Wacholder S, Manos MM, Scott DR, Sherman ME, Kurman RJ, Glass AG, Anderson SM, Schiffman M. A prospective study of human papillomavirus (HPV) type 16 DNA detection by polymerase chain reaction and its associ- ation with acquisition and persistence of other HPV types. J Infect Dis 2001;183:8 -15.
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Senapati, R., Nayak, B., Kar, S. K., & Dwibedi, B. (2017) · BMC Infectious Diseases · doi:10.1186/s12879-016-2136-4 · Cited by 95 · see citing works
“[38], in a study of 106 cervical cancer patients receiving radiation therapy, found that multiple-type HPV was an independent poor prognostic factor.”
Background
- Authors
- Bachtiary, B., Obermair, A., Dreier, B., Birner, P., Breitenecker, G., Knocke, T., Selzer, E., & Pötter, R.
- Affiliations
- University of Vienna (AT)
- Corresponding author
- Bachtiary, Barbara
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2002-10-22
- Volume
- 102
- Issue
- 3
- Pages
- 237-243
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2022810092
- Cited by
- 101
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 7 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 3 · 2012: 4
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien (1629)
- Jubiläumsfonds der Oesterreichischen Nationalbank (8666)
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Keywords
- multiple HPV infection, human papillomavirus, cervical cancer, definitive radiotherapy, HPV genotyping, HPV16, HPV 18, progression-free survival, prognostic factors, treatment response, persistent disease
- MeSH terms
- Adenocarcinoma, Aged, Carcinoma, Squamous Cell, Uterine Cervical Neoplasms, Cloning, Molecular, DNA, Female, Humans, Lymphatic Metastasis, Middle Aged, Neoplasms, Prognosis, Time Factors, Polymerase Chain Reaction, Treatment Outcome, In Situ Hybridization, Sequence Analysis, DNA, Disease-Free Survival, Papillomaviridae
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