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Cited by 329Cervical Cancer and HPV ResearchReproductive tract infections researchGenital Health and Disease

Human Papillomavirus Infection with Multiple Types: Pattern of Coinfection and Risk of Cervical Disease

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Chaturvedi, Anil K., Katki, Hormuzd A., Hildesheim, Allan, Rodríguez, Ana Cecilia, Quint, Wim, Schiffman, Mark, Van Doorn, Leen-Jan, Porras, Carolina +5 more·2011·The Journal of Infectious Diseases
DOI 10.1093/infdis/jiq139PMC PMC3068034
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Abstract

OBJECTIVE: We investigated coinfection patterns for 25 human papillomavirus (HPV) types and assessed the risk conferred by multiple HPV types toward cervical disease. METHODS: Sexually active women (n=5,871) in the NCI-sponsored Costa Rica HPV Vaccine Trial's prevaccination enrollment visit were analyzed. Genotyping for 25 HPVs was performed using SPF(10)/LiPA(25). We calculated odds ratios (ORs) to assess coinfection patterns for each genotype with 24 other genotypes. These ORs were pooled and compared with pair-specific ORs to identify genotype combinations that deviated from the pooled OR. We compared risk of CIN2+/HSIL+between multiple and single infections and assessed additive statistical interactions. RESULTS: Of the 2478 HPV-positive women, 1070 (43.2%) were infected with multiple types. Multiple infections occurred significantly more frequently than predicted by chance. However, this affinity to be involved in a coinfection (pooled OR for 300 type-type combinations=2.2; 95% confidence interval [CI]=2.1-2.4) was not different across HPV type-type combinations. Compared with single infections, coinfection with multiple α9 species was associated with significantly increased risk of CIN2+(OR=2.2; 95% CI=1.1-4.6) and HSIL+(OR=1.6; 95% CI=1.1-2.4). However, disease risk was similar to the sum of estimated risk from individual types, with little evidence for synergistic interactions. CONCLUSIONS: Coinfecting HPV genotypes occur at random and lead to cervical disease independently.

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  • Several reports show the association of multiple infections with cervical cancer.

    “Though there are several reports showing the association of multiple infections with cervical cancer [39, 40] the biological effect of multiple infections on cervical diseases has not yet been established.”

    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 [40]

    The Discussion reports that women with multiple HPV infections had significantly higher risks of CIN2-or-worse and HSIL-or-worse than women with single infections. The Statistical Analyses section shows that these were composite cervical-disease outcomes, not a separate analysis of invasive cervical cancer. Thus the paper supports an association with cervical disease, but not the claim specifically about cervical cancer. (LLM, conf=0.86)

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  1. Vaccarella S, Franceschi S, Snijders PJ, Herrero R, Meijer CJ, Plummer M. Concurrent infection with multiple human papillomavirus types: pooled analysis of the IARC HPV Prevalence Surveys. Cancer Epi- demiol Biomarkers Prev 2010; 19:503-10.
  2. Thomas KK, Hughes JP, Kuypers JM, et al. Concurrent and sequential acquisition of different genital human papillomavirus types. J Infect Dis 2000; 182:1097-102.
  3. Liaw KL, Hildesheim A, Burk RD, et al. A prospective study of human papillomavirus (HPV) type 16 DNA detection by polymerase chain reaction and its association with acquisition and persistence of other HPV types. J Infect Dis 2001; 183:8-15.
  4. Rousseau MC, Pereira JS, Prado JC, Villa LL, Rohan TE, Franco EL. Cervical coinfection with human papillomavirus (HPV) types as a predictor of acquisition and persistence of HPV infection. J Infect Dis 2001; 184:1508-17.
  5. Chaturvedi AK, Myers L, Hammons AF, et al. Prevalence and clustering patterns of human papillomavirus genotypes in multiple infections. Cancer Epidemiol Biomarkers Prev 2005; 14:2439-45.
  6. Mendez F, Munoz N, Posso H, et al. Cervical coinfection with human papillomavirus (HPV) types and possible implications for the pre- vention of cervical cancer by HPV vaccines. J Infect Dis 2005; 192:1158-65.
  7. Plummer M, Schiffman M, Castle PE, Maucort-Boulch D, Wheeler CM. A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion. J Infect Dis 2007; 195:1582-9.
  8. FUTURE II Study Group. Quadrivalent vaccine against human pap- illomavirus to prevent high-grade cervical lesions. N Engl J Med 2007; 356:1915-27.
  9. Kjaer SK, Sigurdsson K, Iversen OE, et al. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against high-grade cervi- cal and external genital lesions. Cancer Prev Res (Phila) 2009; 2:868-78.
  10. Paavonen J, Naud P, Salmeron J, et al. Efficacy of human papilloma- virus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 2009; 374:301-14.
  11. Rousseau MC, Abrahamowicz M, Villa LL, Costa MC, Rohan TE, Franco EL. Predictors of cervical coinfection with multiple human papillomavirus types. Cancer Epidemiol Biomarkers Prev 2003; 12:1029-37.
  12. Paavonen J, Jenkins D, Bosch FX, et al. Efficacy of a prophylactic ad- juvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet 2007; 369:2161-70.
  13. Wheeler CM, Kjaer SK, Sigurdsson K, et al. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in sexually active women aged 16-26 years. J Infect Dis 2009; 199:936-44.
  14. Brown DR, Kjaer SK, Sigurdsson K, et al. The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years. J Infect Dis 2009; 199:926-35.
  15. Herrero R. Human papillomavirus (HPV) vaccines: limited cross- protection against additional HPV types. J Infect Dis 2009; 199: 919-22.
  16. Wentzensen N, Schiffman M, Dunn T, et al. Multiple human papil- lomavirus genotype infections in cervical cancer progression in the study to understand cervical cancer early endpoints and determinants. Int J Cancer 2009; 125:2151-8.
  17. Herrero R, Castle PE, Schiffman M, et al. Epidemiologic profile of type- specific human papillomavirus infection and cervical neoplasia in Guanacaste, Costa Rica. J Infect Dis 2005; 191:1796-807.
  18. Trottier H, Mahmud S, Costa MC, et al. Human papillomavirus in- fections with multiple types and risk of cervical neoplasia. Cancer Epidemiol Biomarkers Prev 2006; 15:1274-80.
  19. de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology 2004; 324:17-27.
  20. Herrero R, Hildesheim A, Rodriguez AC, et al. Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica. Vaccine 2008; 26: 4795-808.
  21. Van Doorn LJ, Molijn A, Kleter B, Quint W, Colau B. Highly effective detection of human papillomavirus 16 and 18 DNA by a testing al- gorithm combining broad-spectrum and type-specific PCR. J Clin Microbiol 2006; 44:3292-8.
  22. Assmann SF, Hosmer DW, Lemeshow S, Mundt KA. Confidence in- tervals for measures of interaction. Epidemiology 1996; 7:286-90.
  23. Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol 2003; 157:218-26.
  24. Koshiol J, Schroeder J, Jamieson DJ, et al. Smoking and time to clearance of human papillomavirus infection in HIV-seropositive and HIV-seronegative women. Am J Epidemiol 2006; 164:176-83.
  25. Xi LF, Koutsky LA, Castle PE, et al. Relationship between cigarette smoking and human papilloma virus types 16 and 18 DNA load. Cancer Epidemiol Biomarkers Prev 2009; 18:3490-6.
  26. Rousseau MC, Villa LL, Costa MC, Abrahamowicz M, Rohan TE, Franco E. Occurrence of cervical infection with multiple human pap- illomavirus types is associated with age and cytologic abnormalities. Sex Transm Dis 2003; 30:581-7.
  27. Xi LF, Edelstein ZR, Meyers C, Ho J, Cherne SL, Schiffman M. Human papillomavirus types 16 and 18 DNA load in relation to coexistence of other types, particularly those in the same species. Cancer Epidemiol Biomarkers Prev 2009; 18:2507-12.

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Authors
Chaturvedi, A. K., Katki, H. A., Hildesheim, A., Rodríguez, A. C., Quint, W., Schiffman, M., Van Doorn, L.-J., Porras, C., Wacholder, S., Gonzalez, P., Sherman, M. E., Herrero, R., & for the CVT Group
Affiliations
  • National Institutes of Health (US)
  • National Cancer Institute (US)
  • Instituto Costarricense de Investigación y Enseñanza en Nutrición y Salud (CR)
  • DDL Diagnostic Laboratory (NL)
ORCID
Venue
The Journal of Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2011-04-01
Volume
203
Issue
7
Pages
910-920
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
DOI
10.1093/infdis/jiq139
PMC
PMC3068034
OpenAlex
W2171917618
Cited by
329
References
0
Citations by year
2026: 21 · 2025: 23 · 2024: 31 · 2023: 16 · 2022: 23 · 2021: 20 · 2020: 18 · 2019: 35 · 2018: 21 · 2017: 16 · 2016: 22 · 2015: 18 · 2014: 18 · 2013: 22 · 2012: 16
FWCI
15.67
Type
journal article
Language
en
Open access
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (n01cp11005-19-0-1)
  • National Cancer Institute (N01‐CP‐11005)
Topics
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
  • Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
  • Health Sciences › Medicine › Surgery › Genital Health and Disease
Keywords
human papillomavirus, HPV co-infection, multiple HPV infection, cervical intraepithelial neoplasia, high-grade squamous intraepithelial lesion, HPV genotypes, synergistic interaction, sexually active women
MeSH terms
Adolescent, Adult, Uterine Cervical Neoplasms, Cervix Uteri, Costa Rica, DNA, Viral, Female, Genotype, Humans, Incidence, Risk Assessment, Papillomaviridae, Papillomavirus Infections, Young Adult

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