Skip to main content
SpringerLink
Log in

Herpes simplex virus type 2 and the risk of cervical cancer: a meta-analysis of observational studies

  • Review
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objectives

To assess whether herpes simplex virus type 2 (HSV-2) infection has an effect on the risk of cervical cancer.

Methods

A systematic literature search of PubMed, Embase, Web of Science, and Scopus from their inception through July 2013 was conducted and reference lists of retrieved articles were reviewed. Information on the characteristics of the included studies, risk estimates, and control for possible confounding factors was extracted independently by two investigators. A random effects model was used to calculate the pooled risk estimates.

Main results

Sixteen articles with 20 studies (14 case control and 6 longitudinal) involving 3,337 patients with cervical cancer were included. Compared with individuals who did not experience HSV-2 infection, the pooled ORs of cervical cancer for individuals with HSV-2 infection were 1.37 (95 % CI 1.12–1.69) for traditional case–control studies and 1.04 (95 % CI 0.82–1.31) for prospective or retrospective nested case–control studies.

Conclusions

Given that a longitudinal study gives a higher level of evidence than a traditional case–control study, the existing observational epidemiological evidence do not support a harmful effect of HSV-2 infection on cervical cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Arbyn M, Castellsagué X, De Sanjosé S, Bruni L, Saraiya M, Bray F, Ferlay J (2011) Worldwide burden of cervical cancer in 2008. Ann Oncol 22(12):2675–2686

    Article  CAS  PubMed  Google Scholar 

  2. Vesco KK, Whitlock EP, Eder M, Burda BU, Senger CA, Lutz K (2011) Risk factors and other epidemiologic considerations for cervical cancer screening: a narrative review for the US Preventive Services Task Force. Ann Intern Med 155(10):698

    Article  PubMed  Google Scholar 

  3. Rawls W, Tompkins W, Figueroa M, Melnick J (1968) Herpesvirus type 2: association with carcinoma of the cervix. Science (New York, NY) 161(847):1255

    Article  CAS  Google Scholar 

  4. Hausen H (1982) Human genital cancer: synergism between two virus infections or synergism between a virus infection and initiating events? Lancet 320(8312):1370–1372

    Article  Google Scholar 

  5. Vonka V, Kanka J, Hirsch I, Zavadova H, Krcmar M, Suchankova A, Rezacova D, Broucek J, Press M, Domorazkova E et al (1984) Prospective study on the relationship between cervical neoplasia and herpes simplex type-2 virus. II. Herpes simplex type-2 antibody presence in sera taken at enrollment. Int J Cancer 33(1):61–66

    Article  CAS  PubMed  Google Scholar 

  6. Lehtinen M, Koskela P, Jellum E, Bloigu A, Anttila T, Hallmans G, Luukkaala T, Thoresen S, Youngman L, Dillner J, Hakama M (2002) Herpes simplex virus and risk of cervical cancer: a longitudinal, nested case-control study in the nordic countries. Am J Epidemiol 156(8):687–692

    Article  PubMed  Google Scholar 

  7. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15):2008–2012

    Article  CAS  PubMed  Google Scholar 

  8. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188. doi:10.1016/0197-2456(86)90046-2

    Article  CAS  PubMed  Google Scholar 

  9. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ (Clinical research ed) 327(7414):557–560. doi:10.1136/bmj.327.7414.557327/7414/557

    Article  Google Scholar 

  10. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  CAS  PubMed  Google Scholar 

  11. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L (2006) Comparison of two methods to detect publication bias in meta-analysis. JAMA 295(6):676–680. doi:10.1001/jama.295.6.676

    Article  CAS  PubMed  Google Scholar 

  12. Arnheim Dahlstrom L, Andersson K, Luostarinen T, Thoresen S, Ogmundsdottir H, Tryggvadottir L, Wiklund F, Skare GB, Eklund C, Sjolin K, Jellum E, Koskela P, Wadell G, Lehtinen M, Dillner J (2011) Prospective seroepidemiologic study of human papillomavirus and other risk factors in cervical cancer. Cancer Epidemiol Biomark Prev 20(12):2541–2550. doi:10.1158/1055-9965.epi-11-0761

    Article  Google Scholar 

  13. Chaouki N, Bosch FX, Muñoz N, Meijer CJ, El Gueddari B, El Ghazi A, Deacon J, Castellsagué X, Walboomers JM (1998) The viral origin of cervical cancer in Rabat, Morocco. Int J Cancer 75(4):546–554

    Article  CAS  PubMed  Google Scholar 

  14. Chichareon S, Herrero R, Muñoz N, Bosch FX, Jacobs MV, Deacon J, Santamaria M, Chongsuvivatwong V, Meijer CJ, Walboomers JM (1998) Risk factors for cervical cancer in Thailand: a case-control study. J Natl Cancer Inst 90(1):50–57

    Article  CAS  PubMed  Google Scholar 

  15. Choi NW, Shettigara PT, Abu-Zeid HA, Nelson NA (1977) Herpesvirus infection and cervical anaplasia: a seroepidemiological study. Int J Cancer 19(2):167–171

    Article  CAS  PubMed  Google Scholar 

  16. Eluf-Neto J, Booth M, Muñoz N, Bosch F, Meijer C, Walboomers J (1994) Human papillomavirus and invasive cervical cancer in Brazil. Br J Cancer 69(1):114

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Ferrera A, Baay MF, Herbrink P, Figueroa M, Velema JP, Melchers WJ (1997) A sero-epidemiological study of the relationship between sexually transmitted agents and cervical cancer in Honduras. Int J Cancer 73(6):781–785

    Article  CAS  PubMed  Google Scholar 

  18. Lehtinen M, Hakama M, Aaran RK, Aromaa A, Knekt P, Leinikki P, Maatela J, Peto R, Teppo L (1992) Herpes simplex virus type 2 infection and cervical cancer: a prospective study of 12 years of follow-up in Finland. Cancer Causes Control 3(4):333–338

    Article  CAS  PubMed  Google Scholar 

  19. Lehtinen M, Dillner J, Knekt P, Luostarinen T, Aromaa A, Kirnbauer R, Koskela P, Paavonen J, Peto R, Schiller JT, Hakama M (1996) Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study. BMJ (Clinical research ed) 312(7030):537–539

    Article  CAS  Google Scholar 

  20. Muñoz N, Bosch F, De Sanjosé S, Tafur L, Izarzugaza I, Gili M, Viladiu P, Navarro C, Martos C, Ascunce N (1992) The causal link between human papillomavirus and invasive cervical cancer: a population-based case–control study in colombia and Spain. Int J Cancer 52(5):743–749

    Article  PubMed  Google Scholar 

  21. Munoz N, Kato I, Bosch FX, De Sanjose S, Sundquist VA, Izarzugaza I, Gonzalez LC, Tafur L, Gili M, Viladiu P et al (1995) Cervical cancer and herpes simplex virus type 2: case-control studies in Spain and Colombia, with special reference to immunoglobulin-G sub-classes. Int J Cancer 60(4):438–442

    Article  CAS  PubMed  Google Scholar 

  22. Ngelange C, Muñoz N, Bosch FX, Festin MR, Deacon J, Jacobs MV, Santamaria M, Meijer CJ, Walboomers JM (1998) Causes of cervical cancer in the Philippines: a case–control study. J Natl Cancer Inst 90(1):43–49

    Article  Google Scholar 

  23. Peng HQ, Liu SL, Mann V, Rohan T, Rawls W (1991) Human papillomavirus types 16 and 33, herpes simplex virus type 2 and other risk factors for cervical cancer in Sichuan Province, China. Int J Cancer 47(5):711–716

    Article  CAS  PubMed  Google Scholar 

  24. Perez LO, Barbisan G, Abba MC, Laguens RM, Dulout FN, Golijow CD (2006) Herpes simplex virus and human papillomavirus infection in cervical disease in Argentine women. Int J Gynecol Pathol 25(1):42–47

    Article  PubMed  Google Scholar 

  25. Santos C, Munoz N, Klug S, Almonte M, Guerrero I, Alvarez M, Velarde C, Galdos O, Castillo M, Walboomers J (2001) HPV types and cofactors causing cervical cancer in Peru. Br J Cancer 85(7):966

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Vonka V, Kanka J, Jelinek J, Subrt I, Suchanek A, Havrankova A, Vachal M, Hirsch I, Domorazkova E, Zavadova H et al (1984) Prospective study on the relationship between cervical neoplasia and herpes simplex type-2 virus. I. Epidemiological characteristics. Int J Cancer 33(1):49–60

    Article  CAS  PubMed  Google Scholar 

  27. Lehtinen M, Hakama M, Knekt P, Heinonen PK, Lehtinen T, Paavonen J, Teppo L, Leinikki P (1989) Lack of serum antibodies to the major HSV-2 specified DNA-binding protein before diagnosis of cervical neoplasia. J Med Virol 27(2):131–136

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

We declare we have no conflict of interest. No funding received for this systematic review.

Author information

Authors and Affiliations

  1. School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan, 430030, People’s Republic of China

    Shiyi Cao, Yong Gan, Xiaoxin Dong & Zuxun Lu

Authors
  1. Shiyi Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaoxin Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zuxun Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zuxun Lu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cao, S., Gan, Y., Dong, X. et al. Herpes simplex virus type 2 and the risk of cervical cancer: a meta-analysis of observational studies. Arch Gynecol Obstet 290, 1059–1066 (2014). https://doi.org/10.1007/s00404-014-3365-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-014-3365-7

Keywords

Search

Navigation