General introduction and thesis outline 15 1 adenocarcinoma in situ (AIS), which is considered the glandular counterpart of CIN3 and, in contrast to CIN, is not further graded 4, 15. 1.2 HPV-MEDIATED CARCINOGENESIS 1.2.1 HUMAN PAPILLOMAVIRUS HPV is a sexually transmitted virus. Persistent infection with HPV is the main aetiologic factor in the development of cervical cancer 16-18. The prevalence of HPV infections is highest among young women (18 – 24 years), soon after the onset of sexual activity, and decreases gradually with age 19-21. The life-time risk of acquiring at least one genital HPV infection is around 80% in sexually active women 22, 23. However, most HPV infections are transient and are cleared spontaneously by the immune system within two years 18, 24. Only a small proportion of HPV infections persists and may lead to cancer. Thus, cervical cancer is a rare complication of a rather common viral infection 25. Risk factors for cervical cancer involve an increased likelihood of acquiring and maintaining an HPV infection and include having multiple sex partners, co-infection with human immunodeficiency virus (HIV), tobacco smoking, long-term use of hormonal contraceptives and high parity. Since the discovery of the link between HPV and cervical cancer in 1983 by professor Normal cervix Cervical intraepithelial neoplasia Invasive cancer Infectious viral particles Squamous epithelium Nuclei with episomal viral DNA Normal nuclei Nuclei with integrated viral DNA Overexpression of E6 and E7 Expression of early and late genes Dermis Basal layer Superficial zone Midzone Basement membrane Grade 1 Grade 2 Grade 3 Figure 1.3 Development of cervical cancer through cervical intraepithelial neoplasia. After entering the basal cells of the cervical epithelium, human papillomavirus infection can give rise to premalignant abnormalities represented by cervical intraepithelial neoplasia grade 1, 2 and 3. These lesions can further progress towards invasive cervical cancer, a process that can take up to 20 to 30 years. Adapted from Woodman et al., Nat Rev Cancer, 2007 26.
RkJQdWJsaXNoZXIy MjY0ODMw