Abstract
BACKGROUND: Perineural Invasion (PNI) is a marker of a highly invasive tumor with poor prognosis, but the real influence on the prognosis of cervical cancer is still debated. We aimed to systematically investigate the prognostic impact of PNI in cervical cancer. METHODS: We searched PubMed, Embase, Cochrane databases, and ClinicalTrials.gov from inception to 20 April 2024. Cohort, case-control, and randomized controlled studies reporting the PNI status and survival outcomes of women with cervical cancer were included. Two reviewers extracted data independently and appraised study quality following the PRISMA guideline. The quality of the studies was assessed with Newcastle-Ottawa Scale. Random effect model was used if the heterogeneity was significant (P ≤ 0.1, I(2) ≥ 50%). RESULTS: We included seven retrospective cohort studies (1561 women) in the analysis. PNI was remarkably associated with a worse survival (risk ratio [95% CI]: 2.79 [1.67- 4.66], I(2) = 78% for 5-year overall survival (OS); 2.16 [1.30-3.59], I(2) = 84% for 5-year disease-free survival (DFS)). After multivariate cox regression adjustment, the hazard ratio [95% CI] of PNI was 3.25 [1.09, 9.74] (I(2) = 85%) for OS, and 2.50 [0.66, 9.46] (I(2) = 89%) for DFS. PNI showed positive correlation with higher stage, larger tumor size, lymph node metastasis, deep stromal invasion, lymphovascular invasion, resection margin involvement, and parametrial invasion (P < 0.05). Besides, PNI was associated with higher possibility of adjuvant therapy (risk difference [95% CI]: 0.28 [0.04-0.52], I(2) = 92%), especially for chemoradiation (0.25 [-0.02-0.53], I(2) = 76%). Subgroup analysis showed patients with PNI had poorer prognosis than those without PNI in patients with LNM or large tumor size (P < 0.05). CONCLUSIONS: PNI demonstrated a significant association with reduced overall survival in cervical cancer patients and emerged as a potential independent prognostic indicator, which provided a foundation for future investigations to evaluate the clinical utility of PNI status in guiding therapeutic strategies. TRAIL REGISTRATION: The protocol for this study was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) under identifying number CRD42022315970.