Treatment characteristics, HPV genotype distribution and risk of subsequent disease among women with high-grade cervical intraepithelial neoplasia in Europe: A systematic literature review.

ABSTRACT

INTRODUCTION: High-grade cervical intraepithelial neoplasia (CIN), a premalignant lesion of the uterine cervix, is caused by persistent Human Papillomavirus (HPV) infection. CIN can be identified through screening programs and high-grade CIN is usually treated by ablation or excision. This study aimed to summarize the clinical management and outcomes among women with high-grade CIN in Europe. METHODS: A systematic literature review was conducted to identify treatment methods and their frequency of use, report HPV genotype prevalence and distribution and summarize patterns for subsequent lesions after primary treatment, among women with high-grade CIN in Europe. Embase®, MEDLINE® and Cochrane databases were searched (1st January 2012 to 30th August 2022), along with relevant conference proceedings (2018-2022), inclusive. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) compliant methodology was adopted. Eligibility criteria included non-immunosuppressed female patients with CIN2+ from Europe (published in English). RESULTS: In total, n = 55 studies were included. CIN excisional therapy was the most received treatment approach (15.8-100 %, loop electrosurgical excision procedure/large loop excision of the transformation zone most common), followed by ablative therapies (1-43.3 %, cold coagulation most common). Other approaches included 'wait and watch' (4.8-52.6 %) and hysterectomy (4.8-16.2 %). HPV positivity rates ranged from 67.8-100 % pre-conization and 4.7-32.8 % post-conization. The most prevalent HPV genotypes reported (both pre- and post-treatment) were HPV16 and HPV18. In patients who received excisional or ablative procedures subsequent CIN was most frequently diagnosed ≤6 months after treatment. The overall rate of subsequent CIN reported was 0.5-20.9 %. CONCLUSION: Conization and ablation were the most common techniques, however, these procedures were associated with sub-optimal outcomes. Close clinical follow-up is important due to the risk of subsequent CIN or invasive cancer. This review serves as a reference point for the comparison of future treatment patterns as they evolve across Europe, following improved implementation of prophylactic HPV vaccination and screening.