Dataset Information

High-sensitivity C-reactive Protein and Regression of Low-grade Squamous Intraepithelial Lesion: The Role of Low-grade Inflammation in Cervical Carcinogenesis.

ABSTRACT:

Background

Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP).

Methods

In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model.

Results

During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028).

Conclusions

The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

SUBMITTER: Ahn S

PROVIDER: S-EPMC8593578 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE:To evaluate the risk of progression to high-grade squamous intraepithelial lesion (HSIL) (CIN2-3) or invasive cancer in women with histopathological diagnosis of low-grade squamous intraepithelial lesion (LSIL) (CIN1), managed in a long-term observational approach up to 5 years. DESIGN:Retrospective cohort study. SETTING:Four tertiary referral hospital. PARTICIPANTS:434 women with adequate colposcopy and complete colposcopic charts were included in the present analysis. Women with glandular lesions on the referral cytology or previous diagnosis of cervical dysplasia or invasive cervical cancer or with synchronous vaginal, or with HIV infection or immunodepression were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES:The main study outcome was the rate of progression to histopathological HSIL (CIN2-3) or invasive cancer at any time during 5 years of follow-up. The possible risk factors were also evaluated. As secondary outcome, we analysed the possible risk factors at the 24-month evaluation for histopathological HSIL (CIN2-3) or invasive cancer progression between 2 and 5 years from initial diagnosis. RESULTS:A progression to histopathological HSIL (CIN2-3) was found in a total of 32 (7.4%) cases during 5 years of follow-up. A histopathological diagnosis of HSIL (CIN3) was found in four patients (0.9%) and no case of invasive cancer was detected. High-grade cytology at inclusion and the presence of a positive high-risk human papillomavirus (HR-HPV) DNA test at 2 years from inclusion maintained a significant correlation with the risk of histopathological progression to HSIL (CIN2-3). CONCLUSIONS:The results of our study showed a low rate (7.4%) of histopathological progression to HSIL (CIN2-3) in women with LSIL (CIN1) diagnosis during long-term follow-up up to 5 years. In case of positive HR-HPV DNA test at the 2 years evaluation an excisional treatment could be the preferred choice to prevent progression to HSIL (CIN2-3) in the following years, preferring a continuation of follow-up in case of HR-HPV DNA negative result.

Project description:It is crucial to classify cervical lesions into high-grade squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), as LSILs are conservatively treated by observation, based on an expectation of natural regression, whereas HSILs usually require electrosurgical excision. In the present study, peripheral blood gene expression profiles were analyzed to identify transcriptomic biomarkers distinguishing HSILs from LSILs. A total of 102 blood samples were collected from women with cervical SILs (66 HSIL and 36 LSIL) for microarray hybridization. Candidate gene signatures were identified using AdaBoost algorithms, and a predictive model was constructed using logistic regression to differentiate HSILs from LSILs. To correct for possible bias as a result of the limited sample size and to verify the stability of the predictive model, a two-fold cross validation and null set analysis was conducted over 1,000 iterations. The functions of the transcriptomic biomarkers were then analyzed to elucidate the pathogenesis of cervical SIL. A total of 10 transcriptomic genes (STMN3, TRPC4AP, DYRK2, AGK, KIAA0319L, GRPEL1, ZFC3H1, LYL1, ITGB1 and ARHGAP18) were identified. The predictive model based on the 10-gene panel exhibited well-discriminated power. A cross validation process using known disease status exhibited almost the same performance as that of the predictive model, whereas null-set analysis with randomly reassigned disease status exhibited much lower predictive performance for distinguishing HSILs from LSILs. These biomarkers were involved in the 'Rho GTPase cycle', 'mitochondrial protein import', 'oncogenic MAPK signaling', 'integrin cell surface interaction' and 'signaling by BRAF and RAF fusions'. In conclusion, peripheral blood gene expression analysis is a promising method for distinguishing HSILs from LSILs. The present study proposes 10 candidate genes that could be used in the future as diagnostic biomarkers and potential therapeutic targets for cervical SILs. A simple, non-invasive blood test would be clinically useful in the diagnosis and classification of patients with cervical SILs.