Assessing colposcopic accuracy for high‐grade squamous intraepithelial lesion detection: a retrospective, cohort study

Background Inappropriate management of high-grade squamous intraepithelial lesions (HSIL) may be the result of an inaccurate colposcopic diagnosis. The aim of this study was to assess colposcopic performance in identifying HSIL+ cases and to analyze the associated clinical factors. Methods Records from 1130 patients admitted to Shenzhen Maternal and Child Healthcare Hospital from 12th January, 2018 up until 30th December, 2018 were retrospectively collected, and included demographics, cytological results, HPV status, transformation zone type, number of cervical biopsy sites, colposcopists’ competencies, colposcopic impressions, as well as histopathological results. Colposcopy was carried out using 2011 colposcopic terminology from the International Federation of Cervical Pathology and Colposcopy. Logistic regression modelling was implemented for uni- and multivariate analyses. A forward stepwise approach was adopted in order to identify variables associated with colposcopic accuracy. Histopathologic results were taken as the comparative gold standard. Results Data from 1130 patient records were collated and analyzed. Colposcopy was 69.7% accurate in identifying HSIL+ cases. Positive predictive value, negative predictive value, sensitivity and specificity of detecting HSIL or more (HSIL+) were 35.53%, 64.47%, 42.35% and 77.60%, respectively. Multivariate analysis highlighted the number of biopsies, cytology, and transformation zone type as independent factors. Age and HPV subtype did not appear to statistically correlate with high-grade lesion/carcinoma. Conclusion Evidence presented here suggests that colposcopy is only 69.7% accurate at diagnosing HSIL. Even though not all HSIL will progress into cancer it is considered pre-cancerous and therefore early identification will save lives. The number of biopsies, cytology and transformation zone type appear to be predictors of misdiagnosis and therefore should be considered during clinical consultations and by way of further research.

The CpG island methylator phenotype increases the risk of high-grade squamous intraepithelial lesions and cervical cancer

Background High-risk human papillomavirus (HR-HPV) infection is the main cause of cervical cancer, but additional alterations are necessary for its development. Abnormal DNA methylation has an important role in the origin and dissemination of cervical cancer and other human tumors. In this work, we analyzed the methylation of eight genes (AJAP1, CDH1, CDH13, MAGI2, MGMT, MYOD1, RASSF1A and SOX17) that participate in several biological processes for the maintenance of cell normality. We analyzed DNA methylation by methylation-specific PCR (MSP) and HPV infection using the INNO‑LiPA genotyping kit in 59 samples diagnostic of normal cervical tissue (non-SIL), 107 low-grade squamous intraepithelial lesions (LSILs), 29 high-grade squamous intraepithelial lesions (HSILs) and 51 cervical cancers (CCs). Results We found that all samples of LSIL, HSIL, and CC were HPV-positive, and the genotypes with higher frequencies were 16, 18, 51 and 56. In general, the genes analyzed displayed a significant tendency toward an increase in methylation levels according to increasing cervical lesion severity, except for the CDH13 gene. High CpG island methylator phenotype (CIMP) was associated with a 50.6-fold (95% CI 4.72–2267.3)-increased risk of HSIL and a 122-fold risk of CC (95% CI 10.04–5349.7). Conclusions We found that CIMP high was significantly associated with HSIL and CC risk. These results could indicate that CIMP together with HR-HPV infection and other factors participates in the development of HSIL and CC.

Comparison of Conservative Treatment of Cervical Intraepithelial Lesions with Imiquimod with Standard Excisional Technique Using LLETZ: A Randomized Controlled Trial

(1) Background: There are limited data on the success of conservative treatment of high-grade cervical squamous intraepithelial lesions (HSIL) with imiquimod directly compared to standard of treatment with LLETZ. (2) Methods: Patients aged 18–40 with histological HSIL (with high-grade cervical intraepithelial neoplasia, CIN2p16+ and CIN3), were randomly assigned to treatment with imiquimod or LLETZ. The primary outcome was defined as the absence of HSIL after either treatment modality. The secondary outcomes were the occurrence of side effects. (3) Results: 52 patients were allocated in each group and were similar regarding baseline characteristics. In the imiquimod group, 82.7% of patients completed treatment, which was successful in 51.9%. All patients in the LLETZ group completed treatment, which was successful in 92.3% (p < 0.001). In the subgroup of CIN2p16+ patients, treatment with imiquimod was not inferior to LLETZ (73.9% vs. 84.2%, p = 0.477). During and after treatment, no cases of progression to cancer were observed. Side effects and severe side effects (local and systemic) were more prevalent in the imiquimod than in the LLETZ group (88.5% vs. 44.2% (p-value < 0.001) and 51.9% vs. 13.5% (p-value < 0.001), respectively). (4) Conclusion: Generally, in patients with HSIL, LLETZ remains the gold standard of treatment. However, in a subgroup analysis of patients with CIN2p16+, the success rate was comparable between the two treatment modalities. Due to the prevalence of side effects, the treatment compliance with imiquimod use may, however, present a clinically important issue.