Vulva Cancer risk factors

Vulval cancer is caused by sexually transmitted infections (STIs) - primarily HPV - and is subject to some additional risk factors, including other sexually transmitted infections, other medical conditions, smoking, iatrogenic immunosuppression and other factors.

Vulval cancer risk factors

 
 

Vulva cancer risk and HPV infection

HPV - human papillomavirus - is present in a proportion of vulval tumours, and HPV 16 is the most commonly detected type. 1, 2

About 70-90% of in situ vulval squamous cell carcinoma (SCC) contain HPV DNA, 3 while the detection rate of HPV DNA in invasive vulval SCC is 20-60%. 3, 4,21 HPV is most strongly linked with tumours in younger women, with an 11-fold risk increase reported for vulval intraepithelial neoplasia (VIN) and early-stage cancer in women under the age of 45 with serological evidence of HPV infection, but no increase in women over this age. 5

Four studies have shown that women with a previous cervical cancer or cervical intraepithelial neoplasia grades 3-5 have up to a ten-fold increased risk for vulval cancer. 6, 7,22, 23 However, one study showed no association of a previous diagnosis of invasive or pre-invasive cervical cancer with risk of invasive vulval SCC, after taking into account other risk factors, including sexual behaviour. 24

Increased risks have also been reported for women diagnosed with cancers at other anogenital sites, 8 or with a family history of anogenital cancer or upper aerodigestive SCC. 9,25

Genital warts (associated with infection with HPV 6 and HPV 11) increase risk for vulval cancer. 9-14 Increased risk has also been reported for individuals with a prior SCC of the skin, which may be related to HPV infection. 15

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Vulva cancer risk and other sexually transmitted infections

Presence of antibodies to the herpes simplex virus type 2 in blood samples has been associated with an increased risk of vulval cancer and pre-cancer, after HPV infection is controlled for. 3,9,13,16

There is an increased risk for vulval cancer and pre-cancers in HIV-positive women, with a particularly strong relationship for women under the age of 30. 17, 18

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Vulva cancer risk and other medical conditions

One study has shown a more than three-fold increased risk of vulval and vaginal cancer in women with systemic lupus erythematosus. 26

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Vulva cancer risk and smoking

There is a well-documented association between smoking and risk of vulval SCC, with reported six-fold and three-fold risk increases in current smokers for in situ and invasive tumours, respectively. 3,19

Risk increases with greater intensity and number of years of smoking and remains elevated more than five years after cessation. 3,19 There is a likely interaction between cigarette smoking and HPV infection in risk of vulval cancer, with a 25-fold risk increase reported for women smoking 20 or more cigarettes a day who also have serological evidence of HPV 16 infection. 3

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Iatrogenic immunosuppression and vulva cancer risk

Incidence of vulval cancer has been shown to be increased 100-fold following renal transplants. 20

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Other factors and vulva cancer risk

One study of people hospitalised for psoriasis in Sweden reported that risk of vulval cancer was increased more than three-fold in this group. 27

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References for vulva 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.  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
  4.  Kagie, M.J., et al., Human papillomavirus infection in squamous cell carcinoma of the vulva, in various synchronous epithelial changes and in normal vulvar skin. Gynecol Oncol, 1997. 67(2): p. 178-83
  5.  Basta, A., K. Adamek, and K. Pitynski, Intraepithelial neoplasia and early stage vulvar cancer. Epidemiological, clinical and virological observations. Eur J Gynaecol Oncol, 1999. 20(2): p. 111-4
  6.  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
  7.  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
  8.  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
  9.  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
  10.  Brinton, L.A., et al., Case-control study of cancer of the vulva. Obstet Gynecol, 1990. 75(5): p. 859-66
  11.  Nordenvall, C., et al., Cancer risk among patients with condylomata acuminata. Int J Cancer, 2006. 119(4): p. 888-893
  12.  Friis, S., et al., Cervical intraepithelial neoplasia, anogenital cancer, and other cancer types in women after hospitalization for condylomata acuminata. J Infect Dis, 1997. 175(4): p. 743-8
  13.  Sherman, K.J., et al., Genital warts, other sexually transmitted diseases, and vulvar cancer. Epidemiology, 1991. 2(4): p. 257-62
  14.  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
  15.  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
  16.  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
  17.  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
  18.  Sitas, F., et al., The spectrum of HIV-1 related cancers in South Africa. Int J Cancer, 2000. 88(3): p. 489-92
  19.  Daling, J.R., et al., Cigarette smoking and the risk of anogenital cancer. Am J Epidemiol, 1992. 135(2): p. 180-9
  20.  Penn, I., Cancers of the anogenital region in renal transplant recipients. Analysis of 65 cases. Cancer, 1986. 58(3): p. 611-6
  21.  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
  22.  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
  23.  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
  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.  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
  26.  Parikh-Patel, A. et al., Cancer risk in a cohort of patients with systemic lupus erythematosus (SLE) in California Cancer Causes Control, 2008.
  27.  Boffetta, P. et al., Cancer risk in a population-based cohort of patients hospitalized for psoriasis in Sweden J Invest Dermatol, 2001. 117(6): p. 1531-7