# Prevention strategies for hereditary gynaecological cancer in Lynch syndrome

## TL;DR

This paper reviews prevention strategies for gynaecological cancers in individuals with Lynch syndrome, focusing on surgical, surveillance, and emerging non-invasive methods.

## Contribution

The paper provides an updated overview of evidence-based prevention strategies and highlights novel approaches for gynaecological cancer prevention in Lynch syndrome.

## Key findings

- Risk-reducing hysterectomy with bilateral salpingo-oophorectomy is the most effective intervention but has significant trade-offs.
- Gynaecological surveillance with transvaginal ultrasound and endometrial biopsy lacks strong evidence for mortality reduction.
- Biomarker-based detection, liquid biopsy, and microbiome profiling show promise but require further validation in Lynch syndrome populations.

## Abstract

Lynch syndrome is a hereditary cancer predisposition condition associated with an elevated lifetime risk of colorectal, endometrial, ovarian, and several other malignancies. This review provides an updated overview of evidence-based prevention strategies for gynaecological cancers in patients with Lynch syndrome. Risk-reducing hysterectomy with bilateral salpingo-oophorectomy is the most effective intervention for lowering cancer incidence and mortality, but is associated with surgical morbidity and requires careful consideration of reproductive plans and the adverse consequences of premature menopause. Gynaecological surveillance using transvaginal ultrasound and endometrial biopsy is widely implemented as an alternative; however, available evidence is heterogeneous and indicates no benefit in reducing mortality. Novel approaches—such as biomarker-based detection using DNA methylation analysis of cervicovaginal samples, liquid biopsy techniques, and microbiome profiling—offer promising, non-invasive alternatives but require prospective validation in Lynch-specific populations. Chemoprevention with hormonal agents and aspirin may reduce cancer risk, while vaccine-based prevention strategies are under active investigation. Adoption of a healthy lifestyle is recommended for overall health, although its impact on gynaecological cancer risk in Lynch syndrome remains uncertain. Future research should prioritise prospective trials to establish optimal cancer prevention protocols, validate novel biomarkers and preventive cancer vaccine strategies, and evaluate the long-term effectiveness, acceptability, and cost-effectiveness of combined preventive approaches to improve outcomes in this high hereditary-risk population.