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Clinical Rheumatology

, Volume 30, Issue 5, pp 665–672 | Cite as

Systemic lupus erythematosus, human papillomavirus infection, cervical pre-malignant and malignant lesions: a systematic review

  • Iuri Usêda Santana
  • Alline do Nascimento Gomes
  • Leomar D’Cirqueira Lyrio
  • Maria Fernanda Rios Grassi
  • Mittermayer Barreto SantiagoEmail author
Original Article

Abstract

The purpose of this study was to review and evaluate systematically the scientific evidence on the relationship between systemic lupus erythematosus (SLE), human papillomavirus (HPV) infection, pre-cancerous cervical abnormalities, and cervical cancer. Establishing strict inclusion and exclusion criteria, we performed an extensive search for studies in MEDLINE and BIREME databases to assess the studies that evaluated the frequency of HPV infection, pre-cancerous cervical abnormalities, and cervical cancer in women with SLE. Secondary references were additionally obtained from the included articles. Thirty-three articles met the criteria previously established. Fifteen out of 18 studies that performed cytological analysis showed a higher frequency of squamous intraepithelial lesions in SLE patients compared with normal women. Moreover, three studies found a higher frequency of high-grade squamous intraepithelial lesions. Additionally, it was observed that women with SLE had a higher frequency of HPV infection, confirmed by molecular biology techniques. Curiously, despite the above findings, no increased frequency of cervical cancer was observed in the majority of the studies which addressed this issue. Five studies observed a relationship between cervical abnormalities and previous use of immunosuppressive drugs. This review suggests that SLE patients seem not to be at increased risk for developing cervical cancer; however, they should be considered at higher risk for HPV infection and cervical dysplasia than the general population. Thus, gynecological visits at shorter intervals seem to be a reasonable approach for those patients.

Keywords

Cancer Cervical intraepithelial neoplasia Dysplasia Human papillomavirus Squamous intraepithelial lesion Systemic lupus erythematosus 

Notes

Acknowledgements

M.B.S. is currently receiving a scholarship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and FIDEPS.

Disclosures

None

References

  1. 1.
    Shukla S, Bharti AC, Mahata S, Hussain S, Kumar R, Hedau S et al (2009) Infection of human papillomaviruses in cancers of different human organ sites. Indian J Med Res 130(3):222–233PubMedGoogle Scholar
  2. 2.
    Grm HS, Bergant M, Banks L (2009) Human papillomavirus infection, cancer & therapy. Indian J Med Res 130(3):277–285PubMedGoogle Scholar
  3. 3.
    Hsueh PR (2009) Human papillomavirus, genital warts, and vaccines. J Microbiol Immunol Infect 42(2):101–106PubMedGoogle Scholar
  4. 4.
    Bosch FX, Lorincz A, Munoz N, Meijer CJ, Shah KV (2002) The causal relation between human papillomavirus and cervical cancer. J Clin Pathol 55(4):244–265PubMedGoogle Scholar
  5. 5.
    Ganguly N, Parihar SP (2009) Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis. J Biosci 34(1):113–123PubMedCrossRefGoogle Scholar
  6. 6.
    Mendonça FMSF, Barbosa AD, Mendonça MSF, Duarte AP (2007) Papilomavírus humano (HPV) no lúpus eritematoso sistêmico (LES). Temas de Reumatologia Clínica 8(1):15–19Google Scholar
  7. 7.
    Abu-Shakra M, Gladman DD, Urowitz MB (1996) Malignancy in systemic lupus erythematosus. Arthritis Rheum 39(6):1050–1054PubMedCrossRefGoogle Scholar
  8. 8.
    Mellemkjaer L, Andersen V, Linet MS, Gridley G, Hoover R, Olsen JH (1997) Non-Hodgkin's lymphoma and other cancers among a cohort of patients with systemic lupus erythematosus. Arthritis Rheum 40(4):761–768PubMedCrossRefGoogle Scholar
  9. 9.
    Pettersson T, Pukkala E, Teppo L, Friman C (1992) Increased risk of cancer in patients with systemic lupus erythematosus. Ann Rheum Dis 51(4):437–439PubMedCrossRefGoogle Scholar
  10. 10.
    Sultan SM, Ioannou Y, Isenberg DA (2000) Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long-term review. Rheumatol (Oxford) 39(10):1147–1152CrossRefGoogle Scholar
  11. 11.
    Ramsey-Goldman R, Mattai SA, Schilling E, Chiu YL, Alo CJ, Howe HL et al (1998) Increased risk of malignancy in patients with systemic lupus erythematosus. J Investig Med 46(5):217–222PubMedGoogle Scholar
  12. 12.
    Tarr T, Szekanecz E, Zeher M, Szegedi G, Kiss E (2006) The occurrence of malignancies in a Hungarian lupus population. Orv Hetil 147(46):2229–2233PubMedGoogle Scholar
  13. 13.
    Lewis RB, Castor CW, Knisley RE, Bole GG (1976) Frequency of neoplasia in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 19(6):1256–1260PubMedCrossRefGoogle Scholar
  14. 14.
    Pryor B, Bologna S, Ernst C, Michalski S, Kahl L (1993) Risk of malignancy in cyclophosphamide-treated SLE patients. Arthritis Rheum 36:S91Google Scholar
  15. 15.
    Lima FR, Guerra D, Sella EMC, Tacla M, Fonseca AM, Bonfa E (1998) Systemic lupus erythematosus and cervical intraepithelial neoplasia. Arthritis Rheum 41(9):S202Google Scholar
  16. 16.
    Sayag-Boukris V, Menkes CJ, Charrier A, Jullian E, Coste J, Landowski P et al (1996) Risk of genital cancer in women with systemic lupus erythematosus. Arthritis Rheum 39:S213Google Scholar
  17. 17.
    Dhar JP, Kmal D, Singh G, Christianson C, Poland-Laken M, Ager J et al (1996) Cervical dysplasia in women with lupus. Arthritis Rheum 39:S69Google Scholar
  18. 18.
    Russomano FB, Serzedello MA, Reis AFF, Horta ALA, Papi JAS, Sanches LR (1986) Doenças do tecido conjuntivo: grupo de alto risco para neoplasia cervical uterina? Rev Bras Ginecol Obstet 8:224Google Scholar
  19. 19.
    Solomon D, Davey D, Kurman R, Moriarty A, O’Connor D, Prey M et al (2002) The 2001 Bethesda system: terminology for reporting results of cervical cytology. JAMA 287(16):2114–2119PubMedCrossRefGoogle Scholar
  20. 20.
    Tam LS, Chan AY, Chan PK, Chang AR, Li EK (2004) Increased prevalence of squamous intraepithelial lesions in systemic lupus erythematosus: association with human papillomavirus infection. Arthritis Rheum 50(11):3619–3625PubMedCrossRefGoogle Scholar
  21. 21.
    Bateman H, Yazici Y, Leff L, Peterson M, Paget SA (2000) Increased cervical dysplasia in intravenous cyclophosphamide-treated patients with SLE: a preliminary study. Lupus 9(7):542–544PubMedCrossRefGoogle Scholar
  22. 22.
    Nath R, Mant C, Luxton J, Hughes G, Raju KS, Shepherd P et al (2007) High risk of human papillomavirus type 16 infections and of development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients. Arthritis Rheum 57(4):619–625PubMedCrossRefGoogle Scholar
  23. 23.
    Berthier S, Mougin C, Vercherin P, Desmurs H, Gil H, de Wazieres B et al (1999) Does a particular risk associated with papillomavirus infections exist in women with lupus? Rev Méd Interne 20(2):128–132PubMedCrossRefGoogle Scholar
  24. 24.
    Barros BRC, Matschinske R, Silva MB, Skare TL (2007) Prevalence of abnormal pap smears in patients with systemic lupus erythematosus. Rev Bras Reumatol 47(5):325–329CrossRefGoogle Scholar
  25. 25.
    Dhar JP, Essenmacher L, Ager J, Sokol RJ (2005) Ominous cervical cytopathology in women with lupus. Int J Gynaecol Obstet 89(3):295–296PubMedCrossRefGoogle Scholar
  26. 26.
    Tam LS, Chan PK, Ho SC, Yu MM, Yim SF, Cheung TH et al (2010) Natural history of cervical papilloma virus infection in systemic lupus erythematosus—a prospective cohort study. J Rheumatol 37(2):330–340PubMedCrossRefGoogle Scholar
  27. 27.
    Febronio MV, Pereira RM, Bonfa E, Takiuti AD, Pereyra EA, Silva CA (2007) Inflammatory cervicovaginal cytology is associated with disease activity in juvenile systemic lupus erythematosus. Lupus 16(6):430–435PubMedCrossRefGoogle Scholar
  28. 28.
    Black KA, Zilko PJ, Dawkins RL, Armstrong BK, Mastaglia GL (1982) Cancer in connective tissue disease. Arthritis Rheum 25(9):1130–1133PubMedCrossRefGoogle Scholar
  29. 29.
    Nived O, Bengtsson A, Jonsen A, Sturfelt G, Olsson H (2001) Malignancies during follow-up in an epidemiologically defined systemic lupus erythematosus inception cohort in southern Sweden. Lupus 10(7):500–504PubMedCrossRefGoogle Scholar
  30. 30.
    Bjornadal L, Lofstrom B, Yin L, Lundberg IE, Ekbom A (2002) Increased cancer incidence in a Swedish cohort of patients with systemic lupus erythematosus. Scand J Rheumatol 31(2):66–71PubMedCrossRefGoogle Scholar
  31. 31.
    Ragnarsson O, Grondal G, Steinsson K (2003) Risk of malignancy in an unselected cohort of Icelandic patients with systemic lupus erythematosus. Lupus 12(9):687–691PubMedCrossRefGoogle Scholar
  32. 32.
    Bernatsky S, Boivin JF, Joseph L, Rajan R, Zoma A, Manzi S et al (2005) An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum 52(5):1481–1490PubMedCrossRefGoogle Scholar
  33. 33.
    Chun BC, Bae SC (2005) Mortality and cancer incidence in Korean patients with systemic lupus erythematosus: results from the Hanyang lupus cohort in Seoul, Korea. Lupus 14(8):635–638PubMedCrossRefGoogle Scholar
  34. 34.
    Parikh-Patel A, White RH, Allen M, Cress R (2008) Cancer risk in a cohort of patients with systemic lupus erythematosus (SLE) in California. Cancer Causes Control 19(8):887–894PubMedCrossRefGoogle Scholar
  35. 35.
    Kang KY, Kim HO, Yoon HS, Lee J, Lee WC, Ko HJ et al (2010) Incidence of cancer among female patients with systemic lupus erythematosus in Korea. Clin Rheumatol 29(4):381–388PubMedCrossRefGoogle Scholar
  36. 36.
    Cibere J, Sibley J, Haga M (2001) Systemic lupus erythematosus and the risk of malignancy. Lupus 10(6):394–400PubMedCrossRefGoogle Scholar
  37. 37.
    Ognenovski VM, Marder W, Somers EC, Johnston CM, Farrehi JG, Selvaggi SM et al (2004) Increased incidence of cervical intraepithelial neoplasia in women with systemic lupus erythematosus treated with intravenous cyclophosphamide. J Rheumatol 31(9):1763–1767PubMedGoogle Scholar
  38. 38.
    Nyberg G, Eriksson O, Westberg NG (1981) Increased incidence of cervical atypia in women with systemic lupus erythematosus treated with chemotherapy. Arthritis Rheum 24(5):648–650PubMedCrossRefGoogle Scholar
  39. 39.
    Blumenfeld Z, Lorber M, Yoffe N, Scharf Y (1994) Systemic lupus erythematosus: predisposition for uterine cervical dysplasia. Lupus 3(1):59–61PubMedCrossRefGoogle Scholar
  40. 40.
    Dhar JP, Kmak D, Bhan R, Pishorodi L, Ager J, Sokol RJ (2001) Abnormal cervicovaginal cytology in women with lupus: a retrospective cohort study. Gynecol Oncol 82(1):4–6PubMedCrossRefGoogle Scholar
  41. 41.
    Mercado U (2009) Squamous intraepithlelial lesions in women's lupus. Ginecol Obstet Méx 77(9):423–427PubMedGoogle Scholar
  42. 42.
    Russomano FB, Serzedello MA, Reis AFF, Horta ALA, Papi JAS, Sanches LR (1989) Involved factors in the association lupus erythematosus-cervical neoplasia. Rev Bras Ginecol Obstet 11(12):238–242Google Scholar
  43. 43.
    Kay S, Frable WJ, Hume DM (1970 Nov) Cervical dysplasia and cancer developing in women on immunosuppression therapy for renal homotransplantation. Cancer 26(5):1048–1052PubMedCrossRefGoogle Scholar
  44. 44.
    Balofsky A, Agmon-Levin N, Shoenfeld Y (2010) The new H1N1 and HPV vaccines and old fears. Curr Opin Rheumatol 22(4):431–436PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2010

Authors and Affiliations

  • Iuri Usêda Santana
    • 1
  • Alline do Nascimento Gomes
    • 1
  • Leomar D’Cirqueira Lyrio
    • 1
  • Maria Fernanda Rios Grassi
    • 2
  • Mittermayer Barreto Santiago
    • 1
    • 3
    Email author
  1. 1.Escola Bahiana de Medicina e Saúde PúblicaSalvadorBrazil
  2. 2.Centro de Pesquisas Gonçalo Moniz/Fundação Oswaldo CruzSalvadorBrazil
  3. 3.Serviço de Reumatologia do Hospital do Santa IzabelSalvadorBrazil

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