Association of Sexual Behaviour and Oral Contraceptive Use with Cervical Neoplasia

Cervical cancer remains the fourth most common cancer in women worldwide. It is associated with high mortality even if much progress has been made in its prevention and treatment. The fact that the necessary cause of cervical cancer is sexually transmitted human papillomavirus (HPV) infection makes it complicated because there are many other sexually associated factors which amplify the risk of HPV infection, such as Chlamydia trachomatis infection, a high number of sexual partners and use of hormonal contraceptives instead of condoms. These factors may put young girls and women at reproductive age at risk of pre-cancerous cervical lesions and cancer.

There is ample evidence of how HPV and Chlamydia increase the risk of cervical cancer, whereas the result of research on the use of hormonal/oral contraceptives is mostly contrasting. The reasons for this could also be due to the duration of contraceptive use in addition to the contraceptive’s hormonal composition and the relative decrease of condom use.

The general aim of this thesis was to find out what role does use of oral contraceptives (OCs) play in cervical neoplastic changes. The required information was taken from the PATRICIA trial of HPV16/18 vaccine efficacy, followed up for 4 years, a cluster randomised trial on the effectiveness of different HPV vaccination strategies and Finnish Student Health Service (FSHS) and Finnish Maternity Cohort (FMC) serum bank. Four peer-reviewed studies are included in the dissertation. In Study I, we assessed the risk between persistent HPV infection and duration of oral contraceptive use among the women who visited the Finnish Student Health Service (FSHS). Long-term use of oral contraceptives was associated with HPV seropositivity, a surrogate of persistent HPV infection.

In Study II, we evaluated the risk of cervical atypia in oral contraceptive users among the women participating in the control arm of the PATRICIA trial of HPV16/18 vaccine efficacy. We found no increased risk of cervical atypia in oral contraceptive users compared to non-users. Instead, the established use of oral contraceptives was protective against cervical atypia compared to non-users of oral contraception.

Study III examined the risk of cervical atypia associated with the changing interval between menarche and the start of sexual activity among the women participating in the control arm of the PATRICIA trial of HPV16/18 vaccine efficacy. A short interval between menarche and the start of sexual activity was not associated with an increased risk of cervical atypia. However, the risk of cervical atypia due to Chlamydia trachomatis infection was increased when the interval between menarche and the start of sexual activity was short.

In Study IV, we assessed the risk between squamous intraepithelial lesions (SILs) and the combined effect of Chlamydia trachomatis and the duration of oral contraceptive use among the women participating in the community randomised HPV vaccination effectiveness trial in Finland. The risk of squamous intraepithelial lesion was increased in Chlamydia trachomatis positive women who were also using oral contraceptives for 5 or more years.

The findings of this thesis emphasise the importance of sexual health counselling, especially contraceptive counselling, among adolescent and young adult women. Infection with either HPV, Chlamydia trachomatis or both cannot always be treated and cured at once. Some infections persist depending upon the person’s physiological condition and lifestyle factors, such as smoking, multiple sexual partners, parity, use of contraceptive methods and socioeconomic status. The persistence of high-risk HPV infection increases the risk of severe cervical lesions. Even though the progression period of HPV-related cervical cancer is relatively long, the risk is high, especially in those countries where there is no HPV vaccination programme. In this study, we found an increased risk of SILs in women who have Chlamydia trachomatis and have used OCs for 5 or more years in an HPV-vaccinated population. Also, high-risk populations with no HPV vaccination will continue to face an increased burden of cervical cancer. Therefore, proper sexual health counselling needs to be promoted. Prospective studies on the use of oral contraceptives and the risk of cervical neoplasia are needed to further elaborate this association.