Prevention of cervical cancer in countries with high and low incidence of the disease

Abstract: Cervical cancer is to a large extent a preventable disease, through prophylactic human papillomavirus (HPV) vaccination and cervical cancer screening. Still, it is the second most common cancer among women in Argentina, with unchanged mortality rates for the last 30 years, due to the absence of organized screening. In Sweden, with a well-organized screening program, cervical cancer burden is lower; however, the incidence is increasing again. This thesis has explored several aspects of cervical cancer prevention in different settings. The overall aim of this thesis is to improve cervical cancer prevention by contributing knowledge on i) vaccination acceptance, ii) barriers to screening and iii) the risk of recurrent/residual disease among women treated for precancerous lesions. Study I explored HPV vaccination acceptance among 174 young women aged 18-30 years from the Mendoza Province, Argentina, by using a structured questionnaire-based interview technique. HPV vaccination acceptance was at high 95%, and 75% stated that they were also willing to pay for vaccination. A statistically significant positive association was found between acceptance and belief in vaccine safety, and a statistically significant negative association between being a welfare recipient and acceptance if vaccination was not free. Educational campaigns ensuring the safety of vaccines, as well as clarifying other misconceptions are needed. Study II investigated maternal HPV vaccination acceptance among 180 mothers to girls aged 9-15 years from the Mendoza province, Argentina, through use of a structured survey. HPV vaccination acceptance was 90% if it was free of charge, and 60% if it was not free. Being gainfully employed and having a higher disposable household income was significantly associated with acceptance of vaccination if it was not free, which suggests that cost could be an obstacle to catch-up vaccination and may lead to socioeconomic inequalities in uptake. Also, women with prior awareness of cervical cancer were more willing to pay for HPV vaccination, indicating the importance of improving awareness of HPV and its related diseases. Study III explored barriers and facilitators of screening compliance among 1510 women attending cervical cancer screening in Stockholm, Sweden through use of a structured survey. The mean total time and travel costs and direct non-medical cost per attendance were €55.6. Nearly half (44%) of the women did not attend screening within 1 year from their invitation, of which 51% cited difficulties in taking time off work. The most important correlates of higher screening compliance were not needing to take time off work, not having a companion and being of higher HPV knowledge. Increased flexibility by extended opening hours and improved general knowledge of HPV may facilitate screening compliance. Study IV investigated the long-term risk of recurrent or residual disease in relation to surgical margin status among 991 women who had undergone conization treatment of high-grade precancerous lesions at the Karolinska University Hospital in Sweden during 2000-2007. During a median of 10 years follow-up, 12% were diagnosed with residual or recurrent disease, based on data from the Swedish National Cervical Screening Registry. Women with involved margins had significantly worse outcomes compared to women with negative margins. The risk was almost 3-fold higher among women with involved endocervical margins, involved margins and uncertain as to whether these were endocervical or ectocervical, and especially when both margins were involved. These findings suggest that stratified margin status may contribute to the safety of the follow-up surveillance. In conclusion; this thesis provides improved knowledge on what may constitute barriers to HPV vaccination and cervical cancer screening, and delineates possible strategies on how to increase uptake of these prevention strategies. Ensuring the safety of HPV vaccines and educational campaigns on HPV and its related diseases appear important targets for achieving higher uptake. Also, our findings suggest that costs can be a barrier, both in the Argentinean setting, as well as to participation in cervical cancer screening in Sweden. It is thus important that the screening organization facilitates the participation of all women in Sweden, including all socioeconomic groups. Finally, the thesis shows that women treated for precancerous lesions with involved surgical margins are at high-risk of recurrent disease and differential risks could be shown with respect to which margin was affected. Future research should address the accuracy of combining margins status with established followup surveillance.