Recent evidence suggests that a cytology–histology correlation (CHC) with discrepancy detection can both evaluate errors and improve the sensitivity and specificity of the cytologic method. We aimed to analyze the errors in cytologic–histologic discrepancies according to the CHC protocol guideline of the American Society of Cytopathology (2017). This retrospective study included 273 patients seen at the National Medical Research Center of Obstetrics, Gynecology and Perinatology (Moscow, Russia) between January 2019 and September 2021. The patients’ mean age was 34 ± 8.1 years. The cytology–histology agreement was noted in 158 cases (57.9%). Major discrepancies were found in 21 cases (7.6%), while minor discrepancies were noted in 93 cases (34.1%). The reason for 13 (4.8%) discrepancies was a colposcopy sampling error and, in 46 (16.8%) cases, the reason was a Papanicolaou (PAP) test sampling error. The discrepancy between primary and reviewed cytology was due interpretive errors in 13 (4.8%) cases and screening errors in 42 (15.4%) cases. We demonstrated that the ASC guidelines facilitate cervical CHC. A uniform application of these guidelines would standardize cervical CHCs internationally, provide a scope for the inter-laboratory comparison of data, and enhance self-learning and peer learning.

Human papillomavirus (HPV) infection is a major risk factor for cervical cancer, demanding improved diagnostic strategies to distinguish between transient infections and those requiring intervention. Background: This systematic review and meta-analysis evaluated the diagnostic accuracy of HPV L1 immunocytochemistry (ICC) in detecting high-grade cervical intraepithelial neoplasia (CIN2+). Methods: We systematically analyzed data from 15 studies (PROSPERO 2022 CRD42022375916) comprising 3804 cervical smears with varying cytological findings (NILM to ≥ASC-US). Results: The pooled sensitivity for detecting CIN2+ was 80.7% (95% CI: 76.2–84.4%); however, substantial heterogeneity was present (I² = 65.97%, p < 0.001). Similarly, the pooled specificity was 56.9% (95% CI: 49.6–64%), with even higher heterogeneity (I² = 90.46%, p < 0.001). This considerable heterogeneity, which may be attributable to methodological variations or regional differences in HPV prevalence and genotyping, limits the generalizability of these findings. Furthermore, the moderate specificity suggests a high rate of false positives, limiting the clinical utility of HPV L1 ICC as a standalone diagnostic test. Conclusions: In conclusion, although HPV L1 ICC exhibits acceptable sensitivity for detecting CIN2+, its limitations, including low specificity and substantial heterogeneity, necessitate its use as an adjunct to other established diagnostic methods, alongside further research to enhance its diagnostic performance, and necessitate its use as a supplementary test alongside established diagnostic methods, pending further research to refine its clinical utility.

Background/Objectives: Atypical cytological findings in cervical screening, such as ASC-US, ASC-H, and AGC, present a clinical challenge due to their variable risk of underlying high-grade lesions. The precise stratification of this risk is crucial for effective patient management. This study aimed to correlate Bethesda cytology categories with HPV genotyping, including viral load, and histological follow-up to improve risk prediction for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Materials and Methods: In this retrospective single-center study, we analyzed 407 patients with cytological reports of ASC-US, ASC-H, or AGC. All patients underwent HPV DNA testing with genotyping for 21 types, with viral load quantification for HPV16/18, and subsequent histological verification. Statistical analyses included non-parametric tests, correlation analysis, and multivariate logistic regression to identify independent predictors of CIN2+. Results: The prevalence of CIN2+ differed significantly among the cytological categories: 23.2% in ASC-US, 47.3% in ASC-H, and 19.5% in AGC. ASC-H and a high HPV16 viral load were identified as independent predictors of CIN2+ in the multivariate analysis. An ASC-H result increased the probability of CIN2+ by 2.5 times (aOR = 2.51; 95% CI: 1.28–4.94). For each 1 log10 increase in HPV16 viral load, the risk of CIN2+ increased by 30% (aOR = 1.30; 95% CI: 1.16–1.46). Stratification of ASC-US cases by HPV16 status revealed a dramatically higher positive predictive value (PPV) for CIN2+ in HPV16-positive patients (66%) compared to HPV16-negative patients (12.6%). The AGC category showed the strongest association with glandular pathology, including adenocarcinoma in situ. Conclusions: The combination of cytological findings and HPV16 viral load provides a powerful model for risk stratification. An ASC-H result is a strong independent risk marker, while the clinical significance of ASC-US is fundamentally determined by HPV16 status. These findings advocate for a risk-based management algorithm that integrates liquid-based cytology with extended HPV genotyping and viral load assessments to optimize patient triage and follow-up.

Aim. To assess the reproducibility of cytological diagnoses in evaluating liquid cervical smears and immunocytochemical co-expression of p16/Ki-67 using manual and automatic methods. Materials and methods. Cytological smears prepared using the liquid cytology method on the Becton Dickinson device (SurePath technology) were studied. An immunocytochemical study was carried out using a Ventana BenchMark Ultra automatic immunostainer with a commercial CINtec kit (determination of p16/Ki-67 co-expression). In total, 100 cytological slides (50 pairs of Pap-smears and immunocytochemical slides) were studied. The diagnostic kit was reviewed by five cytologists independently, and the cytologic slides were evaluated using four categories according to the Bethesda system (2014) and according to the categories of normal/abnormal. The co-expression of p16/Ki-67 was assessed per the manufacturer's recommendations (Roche) using the manual method (light microscope) and the automatic Vision Cyto Pap ICC system. Statistical processing of the results was performed using the SPSS software package version 26.0.0.0 with the calculation of the reproducibility indices of Cohen's kappa and Fleiss' kappa. Results. When assessing the reproducibility of four categories of cytological diagnoses according to the Bethesda system (2014), Cohen's kappa was 0.0480.265. The overall Fleiss' kappa between all cytologists was 0.103. When only two categories (normal/abnormal) were used, the reproducibility ranged from 0.058 to 0.377. When assessing the co-expression of p16 and Ki-67, Cohen's kappa reproducibility was from 0.196 to 0.574, while the overall Fleiss' kappa was 0.407. When comparing the evaluation results of each of the cytologists with the neural network, Cohen's kappa reproducibility ranged from 0.103 to 0.436. Conclusion. The reproducibility of cytological diagnoses according to the Bethesda system (2014) and two categories (normal/abnormal) based on the Pap smear study was low. Such results are primarily due to a large number of abnormal smears in the study. The immunocytochemical method has diagnosis reproducibility three times higher, indicating the need to measure the co-expression of p16 and Ki-67 to increase the sensitivity and specificity of the cytological method. Similar reproducibility when comparing the manual and automatic evaluation of the "double label" suggests that the neural network algorithm can currently help in decision support rather than replace the cytologist at the diagnostic stage.

The article presents a systematic review of the results of modern clinical studies devoted to the problem of the microbiome and transcriptome in women with cervical intraepithelial neoplasia (CIN). Moderate to severe CIN (CIN II – III) can precede the development of cervical cancer (CC) by several years or even decades. Cervical cancer (CC) is an important global health problem. There is a year-on-year increase in the prevalence of CC. Currently, there are many known risk factors that contribute to the development of CIN and cervical cancer. However, the vaginal and cervical microbiome play an important role in the development and progression of CIN and CC, according to some authors. Thus, the timely detection and treatment of cervical intraepithelial lesion-associated genital infections is now especially important. From these point of view, bacterial vaginosis (BV) is considered an acute problem in gynecological practice, which affects the incidence of precancerous conditions of the cervix. The results of the studies have shown the importance of detailed analysis of the vaginal microbial community, which was performed by the method of next generation sequencing (NGS). These studies were conducted using the NGS method based on the analysis of bacterial 16S rRNA genes, which has a high diagnostic accuracy and allows to determine the verity of the microbial landscape. The study of the transcriptome in women with CIN showed a change in many microRNA molecules, which can become markers of the CIN and cervical cancer upon further study. The introduction of the NGS method into the laboratory diagnostics complex will improve the diagnosis and timely prevent the progression of CIN to cervical cancer.The study of the microbiome of the vaginal biotope and cervical canal will allow to identify the groups of patients at high risk for the progression of precancerous lesions of the cervix and cervical cancer. Transcriptome studies have shown changes in many microRNA molecules (SALL4, FOXO1, HBD-1, HBD-2, HBD-3, LL37, psoriasin and IL-8, etc.) in women with CIN and cervical cancer.

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