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Vaginal Cancer risk factors

This page presents information on the risk factors for vaginal cancer including HPV infection, other sexually transmitted infections, Genital washing, Diethylstilboestrol (DES), trauma and smoking.

Vaginal cancer is caused primarily by infection with the human papillomavirus (HPV) and some other sexually transmitted infections (STIs) but, unlike other reproductive tract cancers – with the exception of cervical cancer and vulval cancer– risk of vaginal cancer is not related to reproductive factors or exogenous hormones.

Human papillomavirus and vaginal cancer risk

HPV is present in the majority of vaginal tumours, and HPV 16 is the most commonly detected type.1,2 According to recent surveys, about 60% of invasive and 80-90% of in situ vaginal squamous cell carcinomas contain HPV DNA.3,18

Presence of HPV16 antibodies increases risk for invasive tumours by up to six times and by 13 times for in situ tumours1,3 A doubling in risk has been reported for in situ but not invasive tumours in women with HPV 18 seropositivity.1,3

Women with a previous cervical cancer or cervical intraepithelial neoplasia have up to a 50-fold increased risk for vaginal cancer.4,5,19-21

Increased risks for vaginal cancer have also been reported for women diagnosed with cancers at other anogenital sites,6 or with a family history of anogenital cancer.3,22

Genital warts (associated with infection with HPV 6 and HPV 11) have been shown to increase risk for in situ vaginal cancer by almost six-fold, but the association with invasive tumours is less clear.23,24

Increased risk is also reported for individuals with a prior SCC of the skin, which may be related to HPV infection.9

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Other sexually transmitted infections, medical conditions and vaginal cancer risk

Presence of antibodies to the herpes simplex virus type 2 in blood samples is associated with an increased risk of vulval and vaginal cancer and pre-cancer, after HPV infection is controlled for.3,7,10,11

There is an increased risk for vaginal cancer and pre-cancer in HIV-positive women, with a particularly strong relationship for women under the age of 30.12,13

One study has shown a more than three-fold increased risk of vaginal and vulval cancers in women with systemic lupus erythematosus.25

Genital washing and vaginal cancer risk

One study has shown that genital washing before and after intercourse can reduce risk of vaginal cancer by two-thirds.24

Diethylstilboestrol (DES) and Vaginal cancer risk

DES was used in the 1940s–60s to prevent miscarriage, and has been linked to risk of clear cell adenocarcinomas of the vagina in daughters of women who were treated with the drug. The risk increase is as great as 40-fold,14 and is highest for women whose mothers were exposed to DES in the first trimester of pregnancy.15

Trauma and Vaginal cancer risk

Trauma due to vaginal prolapse or long-term wearing of vaginal pessaries is a causative factor in a small proportion of SCC of the vagina in elderly women.16

Smoking and Vaginal cancer risk

A recent case-control study reported that current smokers had double the risk of vaginal SCC of non-smokers,3 but this association remains uncertain.8,1724

References for vaginal cancer risk factors

1. Carter, J.J., et al., .Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites. Cancer Res, 2001. 61(5): p. 1934-40
2. Bjorge, T., et al., Prospective seroepidemiological study of role of human papillomavirus in non-cervical anogenital cancers. Bmj, 1997. 315(7109): p. 646-9.
3. Daling, J.R., et al., A population-based study of s quamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol, 2002. 84(2): p. 263-70.
4. Evans, H.S., et al., Second primary cancers after cervical intraepithelial neoplasia III and invasive cervical cancer in Southeast England. Gynecol Oncol, 2003. 90(1): p. 131-6.
5. Viikki, M., E. Pukkala, and M. Hakama, Risk of endometrial, ovarian, vulvar, and vaginal cancers after a positive cervical cytology followed by negative histology. Obstet Gynecol, 1998. 92(2): p. 269-73.
6. Frisch, M., J.H. Olsen, and M. Melbye, Malignancies that occur before and after anal cancer: clues to their etiology. Am J Epidemiol, 1994. 140(1): p. 12-9.
7. Sherman, K.J., et al., Genital warts, other sexually transmitted diseases, and vulvar cancer. Epidemiology, 1991. 2(4): p. 257-62.
8. Brinton, L.A., et al., Case-control study of in situ and invasive carcinoma of the vagina. Gynecol Oncol, 1990. 38(1): p. 49-54.
9. Wassberg, C., et al., Second primary cancers in patients with squamous cell carcinoma of the skin: a population-based study in Sweden. Int J Cancer, 1999. 80(4): p. 511-5.
10. Hildesheim, A., et al., Human papillomavirus type 16 and risk of preinvasive and invasive vulvar cancer: results from a seroepidemiological case-control study. Obstet Gynecol, 1997. 90(5): p. 748-54.
11. Madeleine, M.M., et al., Cofactors with human papillomavirus in a population-based study of vulvar cancer. J Natl Cancer Inst, 1997. 89(20): p. 1516-23.
12. Frisch, M., R.J. Biggar, and J.J. Goedert, Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst, 2000. 92(18): p. 1500-10.
13. Sitas, F., et al., The spectrum of HIV-1 related cancers in South Africa. Int J Cancer, 2000. 88(3): p. 489-92.
14. Hatch, E.E., et al., Cancer risk in women exposed to diethylstilbestrol in utero. Jama, 1998. 280(7): p. 630-4.
15. Herbst, A.L., et al., Risk factors for the development of diethylstilbestrol-associated clear cell adenocarcinoma: a case-control study. Am J Obstet Gynecol, 1986. 154(4): p. 814-22.
16. Schraub, S., et al., Cervical and vaginal cancer associated with pessary use. Cancer, 1992. 69(10): p. 2505-9.
17. Daling, J.R., et al., Cigarette smoking and the risk of anogenital cancer. Am J Epidemiol, 1992. 135(2): p. 180-9.
18. Hampl, M., et al., Effect of human papillomavirus vaccines on vulvar, vaginal, and anal intraepithelial lesions and vulvar cancer. Obstet Gynecol, 2006. 108(6): p. 1361-8.
19. Strander, B., et al., Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study BMJ, 2007. 335(7629): p. 1077.
20. Edgren, G., Sparen, P., Risk of anogenital cancer after diagnosis of cervical intraepithelial neoplasia: a prospective population-based study Lancet Oncol, 2007. 8(4): p. 311-6.
21. Kalliala, I., et al., Risk of cervical and other cancers after treatment of cervical intraepithelial neoplasia: retrospective cohort study. BMJ, 2005. 331(7526): p. 1183-5.
22. Hussain, S.K., et al., Familial clustering of cancer at human papillomavirus-associated sites according to the Swedish Family-Cancer Database Int J Cancer, 2008. 122(8): p. 1873-8.
23. Daling, J.R., et al., A population-based study of squamous cell vaginal cancer: HPV and cofactors Gynecol Oncol, 2002. 84(2): p. 263-70.
24. Madsen, B.S., et al., Risk factors for invasive squamous cell carcinoma of the vulva and vagina--population-based case-control study in Denmark Int J Cancer, 2008. 122(12): p. 2827-34.
25. Parikh-Patel, A., et al., Cancer risk in a cohort of patients with systemic lupus erythematosus (SLE) in California Cancer Causes Control, 2008.

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