Correlation of the HPV 16 Genotype Persistence in Women Undergoing LEEP for CIN3 with the Risk of CIN2+ Relapses in the First 18 Months of Follow-Up: A Multicenter Retrospective Study

Objective: Specific hr-HPV genotypes have different natural histories and different oncogenic capacity. This study aimed to investigate the risk of CIN2+ recurrence of the individual genotypes and evaluate how the duration of HPV persistence influences the risk of developing recurrent 16 cervical dysplasia of high grade (CIN2+).

Methods: Data from patients with persistent HPV infection after primary conization were retrospectively extracted. Kaplan-Meier proportional hazards models were used to evaluate associations between the duration of HPV persistence and the risk of developing recurrent CIN2+. Kruskal-Wallis testing with Dunn's multiple comparison test was used to test whether there was a statistically significant difference in the time to development of tumor recurrences between different genotypes.

Results: Overall, 333 patients met the inclusion criteria. In 285 cases the HPV infection was persistent, in 48 cases (18%) it was transient, i.e., different genotypes after LEEP. Overall were diagnosed 39 relapses (13.7%), 79.5% (31/39 cases) were due to genotype 16, 20.5% (8/39) were linked to the other genotypes. Persistence of genotype 16 showed a 7-fold increased risk of developing a CIN2+ relapse, OR = 7.08 (95%CI: 3.12-16.08). Furthermore, the majority of relapses (38/39) occurred within 24 months of persistence with a cut-off represented by 18 months (p = 0.001) in which the relapse rate is maximum and the most frequently found genotype was the 16th with 31 (79.5%) cases of recurrence. Kruskal-Wallis test with Dunn's multiple comparisons has shown statistically significant difference in the time of development of CIN2 relapses among HPV16 and other genotypes. (p < 0.05). Kaplan-meier analysis has shown statistically significant difference between the time to CIN2+ relapse onset in patients with HPV 16 infection and patients with other hrHPV genotypes. (p < 0.05) Conclusions: the study results suggest that persistent HPV infection after LEEP with the same HR genotype present before surgery represents one of the most important predictive factors of the risk of CIN2+ recurrence. The persistence of HPV16 for the first 18 months strongly correlates with the risk of developing a CIN2+ recurrence.