Age-specific predictors of cervical dysplasia recurrence after primary conization: analysis of 3,212 women

Abstract

Objective: This study aimed to identify predictors of recurrence/persistence of cervical intraepithelial neoplasia grade 2+ (CIN2+) lesion (r-CIN2+) after primary conization. Methods: Retrospective analysis involving all consecutive women having conization for CIN2+ between 1998 and 2018. The risk of r-CIN2+ was assessed using Kaplan-Meier and Cox models. Results: Data of 3,212 women were retrospectively identified. After a mean follow-up of 47 (±22.2) months, 112 (3.5%) patients developed r-CIN2+. Mean time interval between prior conization and diagnosis of r-CIN2+ was 26.2 (±13.2) months. Via multivariate analysis, presence of high-risk human papillomavirus (HPV) types at the time of CIN2+ diagnosis, hazard ratio (HR)=3.40 (95% confidence interval [CI]=1.66-6.95) for HPV16/18 and HR=2.59 (95% CI=1.21-5.55) for HPV types other than 16/18, positive margins at primary conization, HR=4.11 (95% CI=2.04-8.26) and HPV persistence after conization, HR=16.69 (95% CI=8.20-33.9), correlated with r-CIN2+, independently. Considering age-specific HPV types distribution, we observed that HPV16/18 infection correlated to an increased risk of r-CIN2+ only in young women (aged ≤25 years; p=0.031, log-rank test); while in the older population (>25 years) HPV type(s) involved had not impact on r-CIN2+ risk (p>0.200, log-rank test). Conclusion: HPV persistence is the main factor predicting r-CIN2+. Infection from HPV16/18 has a detrimental effect in young women, thus highlighting the need of implementing vaccination against HPV in this population. Further prospective studies are warranted for tailoring clinical decision-making for post-conization follow-up on the basis of risk factors.

Prognostic Significance of Neutrophil/Lymphocytes Ratio (NLR) in Predicting Recurrence of Cervical Dysplasia

“…Accordingly with published and well-accepted results of several studies, we found a strong correlation with diseases recurrence in patients with positive surgical margins at the conization surgical specimen. This finding is consistent with the results of several authors [ 4 – 7 , 20 ] and the evidences of many international guidelines on CIN recurrence-associated risk factors [ 29 ]. In this view, some authors have proposed reconization in case of margins involvement; however, this strategy is still controversial, mainly due to the negative effects on subsequent pregnancies of repeated excisional procedures on the cervix [ 30 , 31 ].…”

“…The high-grade cervical intraepithelial neoplasia (HG-CIN) is characterized by a relatively high potential for recurrences after conservative surgery, being the great majority of these occurring in the first 2 years after treatment but with a significant prevalence up to ten years [ 3 , 6 , 7 ]. Different factors have been extensively demonstrated to be related to the recurrence rate: age of patients at diagnosis, surgical cone margins, and HPV positivity at follow-up [ 3 , 6 , 7 , 20 ]; thus, the topic of predicting or, at least, identifying validated risk factors for recurrences is extremely relevant, both for the clinical and the investigational perspective. In this view, leukocytosis and neutrophilia are among the most frequently encountered alterations in cancer patients, and these findings significantly correlate with advanced disease and, consequently, with prognosis [ 14 , 15 , 16 ].…”

Age, margin status, high‑risk human papillomavirus and cytology independently predict recurrent high‑grade cervical intraepithelial neoplasia up to 6 years after treatment

“…Positive HPV as well as abnormal cytology at 2nd follow-up and at routine follow-up each also showed significant association with detected recurrence in bivariate analysis. The importance of persistent HPV positivity after treatment of high-grade CIN has been emphasized ( 39 ). Patterns of persistent HPV infection after treatment of high-grade CIN were the focus of a previous study ( 9 ) since persistence is considered to be the key contributor of progression to invasive cervical cancer.…”

“…In addition, as part of the participation in the study, but not used for clinical decision-making, clinician-collected cervical samples (Abbott), self-collected vaginal samples (VSS) and urine samples were analyzed for comparative HPV testing at 1st follow-up. The procedure employed a multiplex real-time polymerase chain reaction (PCR) test which detects HPV16, HPV18, as well as other high-risk HPV: 31,33,35,39,45,51,52,56,58,59,66,68. The results of this comparative testing are described in detail in a previous study (25).…”

Clinical Outcomes Associated with Endocervical Glandular Involvement in Patients with Cervical Intraepithelial Neoplasia III

“…The recommended treatment for CIN II+ (CIN II and III) lesions is conization, followed by routine human papillomavirus (HPV) and/or cervical cytology tests [ 2 ]. The suggested risk factors for recurrence after conization are age, margin involvement (MI), high-grade CIN, persistent HPV infection, and glandular involvement (GI) [ 3 , 4 , 5 , 6 , 7 , 8 ]. Glandular involvement (GI) is defined as the presence of squamous intraepithelial lesions in pre-existing glandular structures [ 9 ].…”