Epidemiologic classification of human papillomavirus types associated with cervical cancer
Open accessAbstract
BACKGROUND: Infection with human papilloma virus (HPV) is the main cause of cervical cancer, but the risk associated with the various HPV types has not been adequately assessed. METHODS: We pooled data from 11 case-control studies from nine countries involving 1918 women with histologically confirmed squamous-cell cervical cancer and 1928 control women. A common protocol and questionnaire were used. Information on risk factors was obtained by personal interviews, and cervical cells were collected for detection of HPV DNA and typing in a central laboratory by polymerase-chain-reaction-based assays (with MY09/MY11 and GP5+/6+ primers). RESULTS: HPV DNA was detected in 1739 of the 1918 patients with cervical cancer (90.7 percent) and in 259 of the 1928 control women (13.4 percent). With the GP5+/6+ primer, HPV DNA was detected in 96.6 percent of the patients and 15.6 percent of the controls. The most common HPV types in patients, in descending order of frequency, were types 16, 18, 45, 31, 33, 52, 58, and 35. Among control women, types 16, 18, 45, 31, 6, 58, 35, and 33 were the most common. For studies using the GP5+/6+ primer, the pooled odds ratio for cervical cancer associated with the presence of any HPV was 158.2 (95 percent confidence interval, 113.4 to 220.6). The odds ratios were over 45 for the most common and least common HPV types. Fifteen HPV types were classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82); 3 were classified as probable high-risk types (26, 53, and 66); and 12 were classified as low-risk types (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108). There was good agreement between our epidemiologic classification and the classification based on phylogenetic grouping. CONCLUSIONS: In addition to HPV types 16 and 18, types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 should be considered carcinogenic, or high-risk, types, and types 26, 53, and 66 should be considered probably carcinogenic.
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In some studies, multiple HPV infections were not associated with an increased risk of cervical cancer in women with cytological abnormalities.
“In some studies, multiple HPV infections were not associated with an increased risk of cervical cancer in women with cytological abnormalities [24–26].”
From Comparative evaluation of Allplex HPV28 and Anyplex II HPV28 assays for high-risk HPV genotyping in cervical samples (2025) · cites this paper as [24]
In “Risk Associated with HPV” (page unavailable), the paper reports that the cervical-cancer odds ratio for multiple HPV infection was not significantly different from that for single infection (0.7; 95% CI, 0.4–1.0). The study compared women with histologically confirmed squamous-cell cervical cancer with controls; it does not establish this finding specifically for women with cytological abnormalities. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe role of multiple HPV infections in the progression of cervical disease is still controversial.
“The role of multiple HPV infections in the progression of cervical disease is still controversial.”
From Comparative evaluation of Allplex HPV28 and Anyplex II HPV28 assays for high-risk HPV genotyping in cervical samples (2025) · cites this paper as [24]
The “risk associated with HPV” section examines multiple infections and reports no significantly greater cervical-cancer risk than with a single type. It does not assess progression of cervical disease or say that the role of multiple infections remains controversial (page unavailable in our copy). (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe majority of cervical cancers and their precursor lesions are derived from HPV infections.
“The majority of cervical cancers and their precursor lesions are derived from human papillomavirus (HPV) infections [1].”
From Comparison of Seegene Anyplex II HPV28 assay with BD Onclarity HPV assay for human papillomavirus genotyping (2022) · cites this paper as [1]
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Research works printed but not linked: 30
- Ferlay J, Bray F, Pisani P, Parkin DM. Globocan 2000: cancer incidence, mortality and prevalence worldwide, version 1.0. IARC CancerBase no. 5. Lyons, France: IARC Press, 2001.
- Muñoz N, Bosch FX, de Sanjosé S, et al. The causal link between human papilloma- virus and invasive cervical cancer: a popula- tion-based case-control study in Colombia and Spain. Int J Cancer 1992;52:743-9.
- Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 2002;55:244-65.
- Walboomers JMM, Jacobs MV, Manos MM, et al. Human papillomavirus is a neces- sary cause of invasive cervical cancer world- wide. J Pathol 1999;189:12-9.
- Schiffman MH, Bauer HM, Hoover RN, et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Can- cer Inst 1993;85:958-64.
- Kjaer SK, van den Brule AJC, Bock JE, et al. Human papillomavirus -the most sig- nificant risk determinant of cervical intra- epithelial neoplasia. Int J Cancer 1996;65: 601-6.
- de Villiers E-M. Taxonomic classifica- tion of papillomaviruses. Papillomavirus Rep 2001;12:57-63.
- Jacobs MV, de Roda Husman AM, van den Brule AJC, Snijders PJF, Meijer CJLM, Walboomers JMM. Group-specific differen- tiation between high-and low-risk human papillomavirus genotypes by general primer- mediated PCR and two cocktails of oligonu- cleotide probes. J Clin Microbiol 1995;33: 901-5.
- van den Brule AJ, Pol R, Fransen- Daalmeijer N, Schouls LM, Meijer CJLM, Snijders PJ. GP5+/6+ PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. J Clin Microbiol 2002;40:779-87.
- Davies P, Kornegay J, Iftner T. Current methods of testing for human papillomavi- rus. Best Pract Res Clin Obstet Gynaecol 2001;15:677-700.
- Gravitt PE, Peyton CL, Apple RJ, Wheeler CM. Genotyping of 27 human papillomavi- rus types by using L1 consensus PCR prod- ucts by a single-hybridization, reverse line blot detection method. J Clin Microbiol 1998; 36:3020-7.
- Van Ranst M, Kaplan JB, Burk RD. Phy- logenetic classification of human papillo- maviruses: correlation with clinical mani- festations. J Gen Virol 1992;73:2653-60.
- IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 64. Human papillomaviruses. Lyons, France: International Agency for Research on Can- cer, 1995.
- Chaouki N, Bosch FX, Muñoz N, et al. The viral origin of cervical cancer in Rabat, Morocco. Int J Cancer 1998;75:546-54.
- Bayo S, Bosch FX, de Sanjose S, et al. Risk factors of invasive cervical cancer in Mali. Int J Epidemiol 2002;31:202-9.
- Bosch FX, Muñoz N, de Sanjosé S, et al. Human papillomavirus and cervical intraep- ithelial neoplasia grade III/carcinoma in situ: a case-control study in Spain and Colombia. Cancer Epidemiol Biomarkers Prev 1993;2: 415-22.
- Eluf-Neto J, Booth M, Muñoz N, Bosch FX, Meijer CJLM, Walboomers JMM. Human papillomavirus and invasive cervical cancer in Brazil. Br J Cancer 1994;69:114-9.
- Rolón PA, Smith JS, Muñoz N, et al. Human papillomavirus infection and inva- sive cervical cancer in Paraguay. Int J Cancer 2000;85:486-91.
- Santos C, Muñoz N, Klug S, et al. HPV types and cofactors causing cervical cancer in Peru. Br J Cancer 2001;85:966-71.
- Chichareon S, Herrero R, Muñoz N, et al. Risk factors for cervical cancer in Thailand: a case-control study. J Natl Cancer Inst 1998; 90:50-7.
- Ngelangel C, Muñoz N, Bosch FX, et al. Causes of cervical cancer in the Philippines: a case-control study. J Natl Cancer Inst 1998; 90:43-9.
- Manos MM, Ting Y, Wright DK, Lewis AJ, Broker TR, Wolinsky SM. Use of poly- merase chain reaction amplification for the detection of genital human papillomaviruses. In: Furth M, Greaves M, eds. Cancer cells. Vol. 7. Molecular diagnostics of human can- cer. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 1989:209-14.
- de Roda Husman AM, Walboomers JMM, van den Brule AJC, Meijer CJLM, Snijders PJF. The use of general primers GP5 and GP6 elongated at their 3' ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 1995;76:1057-62.
- Breslow NE, Day NE. Statistical meth- ods in cancer research. Vol. 1. The analysis of case-control studies. Lyons, France: Inter- national Agency for Research on Cancer, 1980. (IARC scientific publications no. 32.)
- de Sanjosé S, Bosch XF, Muñoz N, et al. Screening for genital human papillomavi- rus: results from an international validation study on human papillomavirus sampling techniques. Diagn Mol Pathol 1999;8:26-31.
- Herrero R, Hildesheim A, Bratti C, et al. Population-based study of human papillo- mavirus infection and cervical neoplasia in rural Costa Rica. J Natl Cancer Inst 2000;92: 464-74.
- Durst M, Dzarlieva-Petrusevska RT, Boukamp P, Fusenig NE, Gissmann L. Molec- ular and cytogenetic analysis of immortal- ized human primary keratinocytes obtained after transfection with human papillomavi- rus type 16 DNA. Oncogene 1987;1:251-6.
- Storey A, Pim D, Murray A, Osborn K, Banks L, Crawford L. Comparison of the in vitro transforming activities of human pap- illomavirus types. EMBO J 1988;7:1815-20.
- McDougall JK. Immortalization and transformation of human cells by human papillomavirus. Curr Top Microbiol Immu- nol 1994;186:101-19.
- Kleter B, van Doorn LJ, Schrauwen L, et al. Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identifica- tion of anogenital human papillomavirus. J Clin Microbiol 1999;37:2508-17.
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Background
- Authors
- Muñoz, N., Bosch, F. X., de Sanjosé, S., Herrero, R., Castellsagué, X., Shah, K. V., Snijders, P. J. F., & Meijer, C. J. L. M.
- Affiliations
- Institut Català d'Oncologia (ES)
- Johns Hopkins University (US)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-02-06
- Volume
- 348
- Issue
- 6
- Pages
- 518-527
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2101196984
- Cited by
- 6,249
- References
- 0
- Citations by year
- 2026: 102 · 2025: 155 · 2024: 192 · 2023: 179 · 2022: 193 · 2021: 253 · 2020: 239 · 2019: 257 · 2018: 235 · 2017: 221 · 2016: 272 · 2015: 286 · 2014: 329 · 2013: 359 · 2012: 400
- FWCI
- 163.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, public-domain)
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Keywords
- human papillomavirus, cervical cancer, HPV genotyping, high-risk HPV, low-risk HPV, HPV testing, cervical squamous cell carcinoma, HPV16, HPV 18, HPV 31, HPV 33, HPV35, HPV39, HPV52, HPV58, HPV 59, HPV68, HPV73
- MeSH terms
- Adenocarcinoma, Carcinoma, Squamous Cell, Uterine Cervical Neoplasms, DNA, Viral, Female, Humans, Risk Factors, Prevalence, Odds Ratio, Case-Control Studies, Papillomaviridae
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