Research Themes Womens cancers Cervical cancer and HPV

Cervical cancer is the fourth leading cause of cancer death among women worldwide. It is a significant healthcare problem, particularly in lower- and middle-income countries; almost nine out of ten cervical cancer deaths occur in the less developed regions. Although the Netherlands had a good program for cervical cancer screening we still have 700 new cases every year leading to over 200 deaths. Recently, the Dutch Minister of Health, Welfare and Sports decided to reshape the Dutch screening program for cervical cancer. Testing for high-risk human papillomavirus (hrHPV) will replace cytology testing as the primary screening method. Members of our Women’s cancers research theme have had an important scientific role in the establishment of this revolutionary change in screening. Human papillomavirus is a very common, sexually transmitted virus and 80% of all HPV infections clear within 24 months without clinical signs or symptoms (transient infections). Our group has published extensively on the relation between sexual behavior and HPV infections in young women in the pre-vaccine era. Especially the role of persistence of the HPV infection in relation to the development of the (pre)malignancy was studied by members of our group (Melchers, Bekkers and Massuger).
The main reason for the change from cytology to HPV testing is its higher sensitivity: HPV testing detects high grade precancerous lesions better and earlier than cytology testing does (Int J Cancer 2016). This increases the likelihood of treatment before precancerous lesions transform to the actual invasive cervical cancer. In addition, this high sensitivity and the high negative predictive value of HPV testing make longer screening intervals possible. Members of our group have been important in the scientific comparison of hrHPV detection in physician obtained samples versus self-samples obtained by the patients (Melchers and Bekkers). Also, the evaluation of women’s acceptance of the self-sampling devices has been extensively studied by our group. In a large study we compared a new brush based self-sampler with the already existing lavage based self-sampling device (PROHTECT 3B study). Primary HPV screening leads to increased referral rates for colposcopy and to possible overtreatment of young HPV positive women. Therefore, a positive hrHPV test needs an additional follow-up triage test with greater specificity before referral to the gynecologist (Int J Cancer 2016). The additional value of HPV genotyping and possible triage using DNA methylation markers was studied by members of our group in close cooperation with scientists from VU University Medical Center Amsterdam.