Prognostic factors for spontaneous regression of high-risk human papillomavirus-positive cervical intra-epithelial neoplasia grade 2

Abstract

IntroductionSince the implementation of human papillomavirus (HPV)-based screening for cervical cancer, the majority of cervical intra-epithelial neoplasia grade 2 (CIN2) lesions are high-risk (hr)HPV positive. Evidence on prognostic factors in hrHPV-positive CIN2 is lacking, hampering the individual counseling of women undergoing observation as routine management. The aim of this study is to identify prognostic factors for the spontaneous regression of hrHPV-positive CIN2.MethodsA retrospective cohort study was conducted at the Maastricht University Medical Center, the Netherlands. Women with hrHPV-positive CIN2 who underwent observation between January 1, 2000 and April 30, 2013 were included. Regression was defined as Pap 1/2 cytology (normal or atypical squamous cells of undetermined significance (ASCUS) cytology) or ≤CIN1 histology at the 24 month follow-up and no diagnosis of ≥CIN2 before the 24 month follow-up visit. Potential prognostic factors (HPV-16/18, p16 staining, KI67 staining, age, smoking status, last Pap smear result, multiple CIN2 lesions, oral contraception use, and parity) were assessed using logistic regression analysis.ResultsA total of 56 women were included in the study, of which 34 (61%) showed spontaneous regression of their lesion. Of all studied potential prognostic factors, only not smoking and nulliparity were significantly associated with disease regression (OR 3.84, 95% CI 1.04 to 14.21, and OR 5.00, 95% CI 1.32 to 19.00, respectively, in the univariate analysis). Both effects remained significant after correction for age and HPV-16/18 in a multivariable regression analysis. In women who smoked, disease regression occurred in 10 of 22 women (46%), compared with 16 of 21 women (76%) who did not smoke. In parous women, regression occurred in 12 of 27 women (44%), compared with 16 of 20 nulliparous women (80%).DiscussionSmoking status and parity may influence the likelihood of disease regression in hrHPV-positive CIN2. These factors could be considered in individual patient counseling regarding the choice between immediate treatment or conservative management.

A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival

“…Clinicopathological factors including HPV genotype, tobacco smoking, hormonal contraceptives, socioeconomic aspects, reproductive, and sexual factors have been reported as significant for CIN development [ 63 , 64 , 65 , 66 ]. Yet, only a few studies have investigated potential prognostic markers for CIN regression, and predictive power have been identified for HPV genotype [ 67 ], microbiota [ 68 ], age [ 69 ], parity, and smoking status [ 70 ]. CIN2 is known to have a higher probability of regression, and whether conservative treatment should be recommended for these patients is controversial.…”

Importance of the Immune Microenvironment in the Spontaneous Regression of Cervical Squamous Intraepithelial Lesions (cSIL) and Implications for Immunotherapy

“…This effect might be mediated by lower repetitively exposure of the cervical tissue to HPV and semen, which has an immunosuppressive effect [ 118 ]. Lastly, nulliparous women with cHSIL have a 5 times greater likelihood of spontaneous regression than parous women [ 119 ]. This might be explained by increased hormone levels and weakened immune response during pregnancy and tissue damage of the cervix during vaginal delivery [ 120 , 121 ].…”

HPV conversion rates after LEEP, cold-knife conization, and laser and drug therapy: A 4-year follow-up study

“…Further, several systematic reviews have shown that cytological smears are predictive of high-grade cervical lesions (HSIL/HSIL+). [9,15,16] Hence, post-treatment cytology smears and HPV testing are critical, regardless of the treatment modality, especially in older women whose age over 50 years old. Xiao Li et al suggested that postmenopausal patients with high-grade squamous intermediately lesions should be treated preferentially with cold knife conization.…”

“…Moreover, factors like smoking status, which affects the regression of CIN2 lesions in high-risk HPV-positive patients, were not regarded as. [16] Furthermore, the follow-up period was not long enough to achieve the follow-up endpoint. Therefore, additional clinical manifestations that may have occurred after the follow-up could not be observed.…”