Oncological and reproductive outcomes after treatment of cervical intraepithelial neoplasia and early-stage cervical cancer: an advanced evidence synthesis

Abstract

Introduction: The trade-off between effectiveness and reproductive morbidity of different treatments for cervical intraepithelial neoplasia (CIN) and early-stage cervical cancer is unclear. We aimed to compare the effectiveness, complications and costs associated with various techniques. Methods: We performed a network meta-analysis to compare CIN treatments in terms of oncological and reproductive outcomes. We performed a meta-analysis to calculate the risk of cervical cancer and other human papillomavirus (HPV)-related malignancies after CIN treatments. We performed a cost-effectiveness analysis of CIN treatments. Finally, we performed a meta-analysis to compare fertility-sparing treatments for early-stage cervical cancer in terms of oncological and reproductive outcomes. Results: More radical treatment of CIN decreased risk of treatment failure but increased risk of preterm birth compared with less radical treatment. Women treated for CIN remained at increased risk of cervical cancer for at least 20 years after treatment compared with general population; risk was higher after ablation (ablation vs general population: risk ratio [RR]=4.34 [95% confidence interval 1.77–10.61]) than after excision (excision vs general population: RR=2.04 [1.80–2.31]). Risk of other HPV-related malignancies was also elevated after treatment. Large loop excision of the transformation zone (LLETZ) had balanced effectiveness and reproductive morbidity, and so it was the most cost-effective treatment for young women. However, for women who completed childbearing, both LLETZ and laser conisation were cost-effective alternatives. Finally, we found that more radical fertility-sparing surgery for early-stage cervical cancer decreased risk of recurrence but increased risk of reproductive morbidity compared with less radical surgery. Conclusions: Increasing treatment radicality decreases risk of treatment failure but increases risk of subsequent preterm birth. Before deciding upon treatment method, clinicians and patients should be informed of benefits and risks associated with each technique. LLETZ is the most cost-effective treatment for younger patients, but more radical excision could be considered for older patients.