Towards improved diagnostics and treatment of cervical precancerous lesions

Human papillomavirus (HPV) is a significant risk factor for cervical cancer. While HPV infection is common, few people will go on to develop cancer, and this depends on the HPV type and risk factors. Of all HPV types, HPV16 is the primary cause of cervical cancer. At first, we estimated the association between persistent infection with different HPV types and reproductive and behavioral factors among women referred to colposcopy for abnormal cervical cytology. We found that later age at first intercourse protected against HPV16 infection, while smoking predicted HPV16 positivity among women younger than 45 years. In the following study, we assessed the diagnostics of high-grade cervical lesions when electric impedance spectroscopy (EIS) was used as an adjunct to colposcopy. The ZedScan is a hand-held small spectroscope that helps colposcopists differentiate between high- and low-grade lesions and guides biopsy-taking. Colposcopy is highly subjective, with a relatively low diagnostic accuracy (around 60%). The EIS device was more sensitive but less specific in identifying lesions than traditional colposcopy, regardless of cytology. The increased detection of additional cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was the highest among women with low-grade cytology. Finally, we examined the spontaneous regression of the histologically confirmed CIN2 lesions in a prospective cohort. Over 50% of all CIN2 lesions can regress spontaneously in a few years. Since surgical treatment has been associated with later obstetric complications, women of fertile age could particularly benefit from active surveillance of CIN2 to avoid overtreatment. In a 2-year follow-up study of women aged 30 years or younger, a complete regression occurred in 64% and partial regression in 14%, while 16% progressed to CIN3+. The prognostic factor for regression was high-risk HPV test negativity at baseline, while progression was associated with high-grade referral cytology and large cervical lesions. A better understanding of the role of various risk factor profiles of progression, as well as improving diagnostic methods and treatment options for cervical disease, are highly needed.