The Role of Neutrophil-Lymphocytes Ratio in the Prognosis of CIN2+ Recurrence after Excisional Treatment.

Objectives: The main risk factor involved in CIN2+ recurrence after treatment is the HPV persistent infection. The dysregulation of the immune system permits only HR-HPVs to become persistent infections, to promote cancer development, and to increase the risk of recurrence after treatment. Therefore, there is a shift to a Th2-type cytokine pattern during the carcinogenesis pathway; for this reason, the neutrophil-lymphocytes ratio (NLR) could be a marker of this immunological change. The study aimed to analyse the predictive role of NLR in the recurrence of high-grade CIN (CIN2+) after excisional treatment in a real-world life setting of patients treated for CIN2+.

Design: This study wascross-sectional study.

Participants/materials, setting, methods: We examined a retrospective database of 444 patients, who attended the colposcopy service of our department from 2011 to 2020 due to an abnormal screening Pap smear, and we compared the clinical characteristics to NLR performed at the time of diagnosis. All analysed patients were treated according to an established protocol (colposcopy every 6 months for the first 2 years and every year for over 3 years) and HPV-DNA test and cervical biopsy were performed at entry and the end of follow-up. All patients underwent a blood sample examination, including complete white blood cell counts and collecting neutrophil and lymphocyte values expressed as 103/mL.

Results: The sensitivity (SE) and specificity (SP) of the NLR cut-off point of 1.34 for the diagnosis of CIN2+ recurrence were 0.76 and 0.67, respectively. We found that CIN2+ recurrences were significantly higher in patients with NLR <1.34 (3.7% vs. 0.6%, p = 0.033) and the 5-year recurrence-free survival was higher in patients with NLR ≥1.34 (97% vs. 93%, p = 0.030).

Limitations: Firstly, the retrospective analysis and low incidence of recurrence may limit the conclusions. Second, for the retrospective design of the study, we did not take into consideration the patient's comorbidities and habits (smoking) that may influence the NLR. On the other hand, the median duration of follow-up in our study was 26 months (IQR: 22-31), which fully reflects the incidence of recurrences.

Conclusions: It is well known that CIN2+ lesions are sustained by deregulation of the immune system caused by persistent HPV infection, which may lead to cervical cancer. Among the actors underlying dysregulation of immunity, lymphocytes are involved in the permission of persistent infection and for this reason, NRL could be a reliable and cost-effective biomarker in predicting the risk of recurrence, especially for high-grade cervical lesions.