Risk factors for anogenital cancers in postmenopausal women: the Million Women Study

Thesis

Background: Anal, vulval and vaginal cancers predominantly affect postmenopausal women. Over 85% of registrations occur after the age of 50. Risk factors for these cancers, other than high-risk human papillomaviruses, are not well defined.

Methods: 1.3 million UK women, mostly aged 50-65 at recruitment, were followed for incident anogenital cancer. Cox regression models with age as the underlying time variable were used to calculate adjusted relative risks associated with various lifetime exposures.

Results: 570 anal, 898 vulval, and 170 vaginal cancers were registered over an average 13.8 years of follow-up. History of cervical intraepithelial neoplasia grade 3 (CIN 3) prior to recruitment was associated with a 4-fold increase in risk of anal cancer, a doubling of risk of vulval cancer, and a 7-fold increase in risk of vaginal cancer. Significant associations were also seen for past cervical cytological abnormalities, with an increase in risk of anal cancer for low-grade, and an increase in risk of all three cancers associated with high-grade abnormalities.

Anal cancer risk was also associated with smoking, prior use of oral contraceptives, nulliparity, tubal ligation, and not living with a husband/partner. Risk of vulval cancer was increased in overweight, obese women, and those with a menopause prior to age 50. Risk of vaginal cancer was increased amongst women who were nulliparous, overweight or obese, who had a hysterectomy prior to recruitment, or who were not married or living with a partner.

Conclusions: Despite anatomical proximity and histological similarities of the anogenital tissues, anal, vulval and vaginal cancers have heterogeneous associations with many lifetime exposures, suggesting differences in aetiology. Past high-grade cervical abnormalities are a marker of increased risk of subsequent anogenital cancer, but only a small proportion of women with such a history go on to develop anal, vulval or vaginal cancer later in life.

Authors: Coffey, CJ

• DOI: 10.5287/ora-jne98m1ay
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Subjects: Cancer--Epidemiology