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Accurate segmentation of tissues and lesions is crucial for disease diagnosis, treatment planning, and surgical navigation. Yet, the complexity of medical images presents significant challenges for traditional Convolutional Neural Networks and Transformer models due to their limited receptive fields or high computational complexity. State Space Models (SSMs) have recently shown notable vision performance, particularly Mamba and its variants. However, their feature extraction methods may not be sufficiently effective and retain some redundant structures, leaving room for parameter reduction. In response to these challenges, we introduce a methodology called Rotational Mamba-UNet, characterized by Residual Visual State Space (ResVSS) block and Rotational SSM Module. The ResVSS block is devised to mitigate network degradation caused by the diminishing efficacy of information transfer from shallower to deeper layers. Meanwhile, the Rotational SSM Module is devised to tackle the challenges associated with channel feature extraction within State Space Models. Finally, we propose a weighted multi-level loss function, which fully leverages the outputs of the decoder's three stages for supervision. We conducted experiments on ISIC17, ISIC18, CVC-300, Kvasir-SEG, CVC-ColonDB, Kvasir-Instrument datasets, and Low-grade Squamous Intraepithelial Lesion datasets provided by The Third Affiliated Hospital of Sun Yat-sen University, demonstrating the superior segmentation performance of our proposed RM-UNet. Additionally, compared to the previous VM-UNet, our model achieves a one-third reduction in parameters. Our code is available at https://github.com/Halo2Tang/RM-UNet. [ABSTRACT FROM AUTHOR]

Simple Summary: A colposcopy provides a comprehensive examination of the female genital tract, including the cervix, vagina, and vulva. However, its diagnostic accuracy, especially for vaginal lesions, remains suboptimal due to the challenge in detecting subtle alterations. Integrating artificial intelligence (AI) into colposcopy holds potential to enhance the detection rates of clinically important lesions. Our study pioneered the development of an AI algorithm capable of differentiating low-grade (LSILs) and high-grade (HSILs) squamous intraepithelial lesions in the vagina. The promising results we achieve in differentiating HPV-associated dysplastic lesions demonstrate that AI can significantly address the current challenges in medical practice. There are already promising results when using AI to detect HPV lesions in the cervix and anus, suggesting that in the future, this ubiquitous tool for lesion detection across different anatomical regions could be a reality. The future integration of these technologies into the colposcopy process could revolutionize healthcare, making early detection a reality for women worldwide. Background/Objectives: While human papillomavirus (HPV) is well known for its role in cervical cancer, it also affects vaginal cancers. Although colposcopy offers a comprehensive examination of the female genital tract, its diagnostic accuracy remains suboptimal. Integrating artificial intelligence (AI) could enhance the cost-effectiveness of colposcopy, but no AI models specifically differentiate low-grade (LSILs) and high-grade (HSILs) squamous intraepithelial lesions in the vagina. This study aims to develop and validate an AI model for the differentiation of HPV-associated dysplastic lesions in this region. Methods: A convolutional neural network (CNN) model was developed to differentiate HSILs from LSILs in vaginoscopy (during colposcopy) still images. The AI model was developed on a dataset of 57,250 frames (90% training/validation [including a 5-fold cross-validation] and 10% testing) obtained from 71 procedures. The model was evaluated based on its sensitivity, specificity, accuracy and area under the receiver operating curve (AUROC). Results: For HSIL/LSIL differentiation in the vagina, during the training/validation phase, the CNN demonstrated a mean sensitivity, specificity and accuracy of 98.7% (IC95% 96.7–100.0%), 99.1% (IC95% 98.1–100.0%), and 98.9% (IC95% 97.9–99.8%), respectively. The mean AUROC was 0.990 ± 0.004. During testing phase, the sensitivity was 99.6% and 99.7% for both specificity and accuracy. Conclusions: This is the first globally developed AI model capable of HSIL/LSIL differentiation in the vaginal region, demonstrating high and robust performance metrics. Its effective application paves the way for AI-powered colposcopic assessment across the entire female genital tract, offering a significant advancement in women's healthcare worldwide. [ABSTRACT FROM AUTHOR]

This study evaluates the efficacy and safety of radiofrequency ablation (RFA) in treating low-grade squamous intraepithelial lesions (LSIL) with high-risk human papillomavirus (hrHPV) infection. The clinical data of 100 patients with LSIL and hrHPV infection were retrospectively analyzed. Patients were divided into the RFA group and the 5- aminolevulinic acid photodynamic therapy (ALA-PDT) group according to the treatment protocol, with 50 patients per group. Efficacy, negative hrHPV seroconversion, mental status, treatment satisfaction, and the occurrence of adverse reactions were compared between the two groups. The RFA group had a significantly higher total effective rate (94.00%) than the ALA-PDT group (74.00%). At 3 and 6-month follow-ups, the negative hrHPV seroconversion rate was significantly higher in the RFA group than in the ALA-PDT group (p < 0.05). At 6 months after treatment, the RFA group showed significantly lower Self-Rating Anxiety Scale scores and Self-Rated Depression Scale scores and higher satisfaction compared to the ALA-PDT group (all p < 0.05). The incidence of postoperative complications rate was not significantly different between the RFA group and ALA-PDT group (χ² = 3.184, p = 0.074). RFA is an effective and safe treatment that improves anxiety, depression, and satisfaction in patients with LSIL complicated by hrHPV infection. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to identify the prevalence and distribution of high-risk human papillomavirus (HR-HPV) types among Kazakhstani women with abnormal cervical cytology. Methods: A cross-sectional study was performed from May 2019 to June 2020. Cervical samples were collected from women in the different regions of Kazakhstan. Results: A total of 316 patients' samples were analysed for HR-HPV using real-time multiplex PCR. Cervical cytology abnormalities were reported according to the Bethesda classification. HPV detection by cytology showed a statistically significant association with HPV status and the number of HPV infection types (p < .05). Among women with abnormal cervical cytology, 62.4% were positive for HPV infection of those 79.4% had low-grade squamous intraepithelial lesions (LSIL), and 20.6% had high-grade squamous intraepithelial lesions (HSIL). Among patients with LSIL, 77.4% had HPV16 and 58.8% were infected with HPV18. Among patients with HSIL, 41.2% had HPV18 and 22.6% - HPV16. Conclusions: There is a high prevalence of HR-HPV types among Kazakhstani women with abnormal cervical cytology. The most identified types were HPV16, 18, 31, 33 and 52. There is an emergency need to implement an HPV vaccination program to prevent cervical lesion development. [ABSTRACT FROM AUTHOR]

The aim of the present study was to compare colposcopic biopsy results of women in Turkey with normal cervical cytology and Atypical Squamous Cells of Undetermined Significance (ASCUS) who had human papilloma virus (HPV) genotypes 16, 18 and combined 16/18. The overarching goal was to enhance the existing body of evidence on cervical cancer screening strategies, with an ultimate aim of refining HPV testing guidelines and improving patient management. In this retrospective study, we examined the medical records of 1121 patients from a tertiary health care setting who tested positive for HPV 16, HPV 18 or both, and who exhibited ASCUS or normal Pap smear findings. A detailed review of the patients’ colposcopic biopsy outcomes was conducted, with particular attention to their HPV genotype status and the impact of smoking. The 1121 patients were classified based on HPV genotype into three groups: HPV 16 (78.5%), HPV 18 (15.8%), and co-infection with HPV 16 and 18 (5.7%). On the basis of smear characteristics, patients were categorized as normal (81.4%) and ASCUS (18.2%). Approximately 40% of patients infected with HPV 16, HPV 18 or both with no evidence of intraepithelial lesion or malignancy (NILM) or ASCUS on Pap smear had High-grade Squamous Intraepithelial Lesion cancer on biopsy. Notably, for those with normal smear results, the rate of Low-grade Squamous Intraepithelial Lesion biopsy was approximately 15% higher in the HPV 18 group than the HPV 16 group (59.6% vs. 45.8%; p = 0.023). Smoking prevalence was significantly higher in the co-infected HPV 16/18 group (p = 0.013). This study underscores the importance of vigilant HPV and cytology testing, especially for individuals with HPV 16/18, regardless of normal cytology findings. [ABSTRACT FROM AUTHOR]

AbstractAim This study aimed to identify the prevalence and distribution of high-risk human papillomavirus (HR-HPV) types among Kazakhstani women with abnormal cervical cytology.Methods A cross-sectional study was performed from May 2019 to June 2020. Cervical samples were collected from women in the different regions of Kazakhstan.Results A total of 316 patients’ samples were analysed for HR-HPV using real-time multiplex PCR. Cervical cytology abnormalities were reported according to the Bethesda classification. HPV detection by cytology showed a statistically significant association with HPV status and the number of HPV infection types (p

Background/Objectives: Proficient colposcopy is crucial for the adequate management of cervical cancer precursor lesions; nonetheless its limitations may impact its cost-effectiveness. The development of artificial intelligence models is experiencing an exponential growth, particularly in image-based specialties. The aim of this study is to develop and validate a Convolutional Neural Network (CNN) for the automatic differentiation of high-grade (HSIL) from low-grade dysplasia (LSIL) in colposcopy. Methods: A unicentric retrospective study was conducted based on 70 colposcopy exams, comprising a total of 22,693 frames. Among these, 8729 were categorized as HSIL based on histopathology. The total dataset was divided into a training (90%, n = 20,423) and a testing set (10%, n = 2270), the latter being used to evaluate the model's performance. The main outcome measures included sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and the area under the receiving operating curve (AUC-ROC). Results: The sensitivity was 99.7% and the specificity was 98.6%. The PPV and NPV were 97.8% and 99.8%, respectively. The overall accuracy was 99.0%. The AUC-ROC was 0.98. The CNN processed 112 frames per second. Conclusions: We developed a CNN capable of differentiating cervical cancer precursors in colposcopy frames. The high levels of accuracy for the differentiation of HSIL from LSIL may improve the diagnostic yield of this exam [ABSTRACT FROM AUTHOR]

Introduction: Carcinoma cervix is the most common cancer and the invasive stage of cervical cancer is preceded by pre-invasive phases and all the phases can be picked up and diagnosed by Pap smear. p16INK4 is a tumour suppressor protein which serves as a surrogate marker for the oncogenic activities of Human Papilloma virus and its overexpression is well established in cervical intraepithelial neoplasia (CIN) and invasive cancers. Aim: To evaluate the pattern of cervical cytology at a tertiary care hospital and to correlate the findings with histopathological diagnosis and to determine the importance of p16INK4a as a diagnostic marker of HPV by IHC staining method. Materials and Methods: This is a two year retrospective study done on Pap smears reported between April 2021 to May 2023 in the Department of Pathology, Gayatri Vidya Parishad Institute of Healthcare and Medical Technology, Visakhapatnam. Frequency and percentage statistics was used to present the results. Results: A total of 844 Pap smears were included in the study, out of which 52 were cytologically abnormal. Biopsy was done on 42 cases, out of which 33 cases showed concordance which included18 LSIL, 8 HSIL, 5 squamous cell carcinoma and 2 cases of adenocarcinoma, among them p16INK4a was found to be positive in 6 cases of LSIL, 5 cases of HSIL and 4 cases of SCC and 2 cases of adenocarcinoma. Conclusion: Pap smear is a sensitive and cost effective screening modality for premalignant and malignant lesions of cervix and expression of p16 as IHC marker has the potential to accredit the lesions with an increased risk of progression to high-grade lesions. [ABSTRACT FROM AUTHOR]

Study objective: This study aims to evaluate the role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix. Materials and methods: A total of 95 women participated in this prospective study and were divided into the following groups: 19 healthy subjects (group 1) with normal cervicovaginal smear (CVS) and negative human papillomavirus test (HPV DNA), 19 women with normal cervical biopsy and normal final pathological result of cervical biopsy (group 2), 19 women with low-grade squamous intraepithelial lesion (LSIL) (group 3), 19 women with high-grade squamous intraepithelial lesion (HSIL) (group 4), and 19 women with cervical cancer (group 5). Clinical, demographic, histopathological, and elastographic results were compared between these groups. Results: Comparing groups, age (40.42 ± 8.31 vs. 39.53 ± 8.96 vs. 38.79 ± 9.53 vs. 40.74 ± 7.42 vs. 54.63 ± 12.93, p < 0.001 respectively), gravida (1.74 ± 1.33 vs. 2.16 ± 1.68 vs. 2.21 ± 1.96 vs. 2.53 ± 1.93 vs. 4.63 ± 2.17 p < 0.001 respectively), parity (1.37 ± 0.68 vs. 1.68 ± 1.20 vs. 1.58 ± 1.30 vs. 2.00 ± 1.67 vs. 3.37 ± 1.61, p < 0.001 respectively), and the proportion of patients at menopause (10.5% vs., 15.8% vs. 10.5% vs. 5.3% vs. 57.9%, p < 0.01 respectively), a statistically significant difference was found (Table 1). However, no statistically significant difference was found in the number of abortions, BMI, mode of delivery, smoking, additional disease status, history of surgery, and family history (p > 0.05) (Table 2. As a result of the applied roc analysis, mean cervical elastographic stiffness degree (ESD) was found to be an influential factor in predicting cervical cancer (p < 0.05). The mean cut-off value was 44.65%, with a sensitivity of 94.7% and a specificity of 96.1% (Table 7). Conclusion: Measurement of ESD by elastography is a low-cost, easily applicable, and non-invasive indicator that can distinguish cervical cancer from normal cervical and preinvasive lesions. However, it is unsuitable for determining preinvasive cervical lesions from normal cervix. [ABSTRACT FROM AUTHOR]

ABSTRACT A substantial percentage of the population remains at risk for cervical cancer due to pre-existing human papillomavirus (HPV) infections, despite prophylactic vaccines. Early diagnosis and treatment are crucial for better disease outcomes. The development of new treatments heavily relies on suitable preclinical model systems. Recently, we established a mouse papillomavirus (MmuPV1) model that is relevant to HPV genital pathogenesis. In the current study, we validated the use of Papanicolaou (Pap) smears, a valuable early diagnostic tool for detecting HPV cervical cancer, to monitor disease progression in the MmuPV1 mouse model. Biweekly cervicovaginal swabs were collected from the MmuPV1-infected mice for viral DNA quantitation and cytology assessment. The Pap smear slides were evaluated for signs of epithelial cell abnormalities using the 2014 Bethesda system criteria. Tissues from the infected mice were harvested at various times post-viral infection for additional histological and virological assays. Over time, increased viral replication was consistent with higher levels of viral DNA, and it coincided with an uptick in epithelial cell abnormalities with higher severity scores noted as early as 10 weeks after viral infection. The cytological results also correlated with the histological evaluation of tissues harvested simultaneously. Both immunocompromised and immunocompetent mice with squamous cell carcinoma (SCC) cytology also developed vaginal SCCs. Notably, samples from the MmuPV1-infected mice exhibited similar cellular abnormalities compared to the corresponding human samples at similar disease stages. Hence, Pap smear screening proves to be an effective tool for the longitudinal monitoring of disease progression in the MmuPV1 mouse model.IMPORTANCEPapanicolaou (Pap) smear has saved millions of women's lives as a valuable early screening tool for detecting human papillomavirus (HPV) cervical precancers and cancer. However, more than 200,000 women in the United States alone remain at risk for cervical cancer due to pre-existing HPV infection-induced precancers, as there are currently no effective treatments for HPV-associated precancers and cancers other than invasive procedures including a loop electrosurgical excision procedure (LEEP) to remove abnormal tissues. In the current study, we validated the use of Pap smears to monitor disease progression in our recently established mouse papillomavirus model. To the best of our knowledge, this is the first study that provides compelling evidence of applying Pap smears from cervicovaginal swabs to monitor disease progression in mice. This HPV-relevant cytology assay will enable us to develop and test novel antiviral and anti-tumor therapies using this model to eliminate HPV-associated diseases and cancers.

Cervical cancer ranks as the third most common female cancer in Cape Verde and is the leading cause of cancer-related deaths among women in the country. While Human Papillomavirus (HPV) vaccination, which started in 2021, is anticipated to significantly reduce disease incidence, cervical screening remains crucial for non-vaccinated women. We retrospectively reviewed gynecologic cytology exams and HPV tests performed in Cape Verde between 2017 and April 2023 and processed at IMP Diagnostics. For this study, we considered 13035 women with cytology examinations performed and, 2013 of these, also with an HPV molecular test. Cytology diagnostics comprised 83 % NILM cases; 12 % ASC-US; 2.7 % LSIL; 1.2 % ASC-H; 0.5 % HSIL and 0.1 % SCC. In 505 (25.1 %) high-risk HPV infection was detected. Prevalence of HPV infection varied with age, peaking at young ages - ≤24 years old (55.5 %) and 25-35-year-old women (31.5 %) - and the lowest after 66 years old (9.7 %). Herein we present a comprehensive study regarding Cape Verde's cervical cytology and HPV distribution, aiming to provide a snapshot of the country's cervical cytology results and HPV distribution in recent years. Moreover, these data may contribute to establish a baseline to assess, in the future, the vaccination impact in the country.

Background: Infertility is a widespread global health concern that impacts millions of people of reproductive age worldwide. Statistics indicate that around one in every six individuals of reproductive age experience infertility at some point in their lives. Methods: From May 2022 to October 2022, the Department of Obstetrics and Gynaecology at the National Institute of Medical Sciences & Research in Jaipur conducted a prospective study within a hospital setting. Results: On Liquid-based Pap smear 79.38% patients were present NlLM, 11.88% patients were present ASCUS, 3.75% patients were presenting inflammatory and 3.75% patients were present HSIL & 1.25 of LSIL. Conclusion: Our findings indicate that infertile patients, particularly those with tubal factor infertility, exhibit a higher propensity for cervical cytological abnormalities. Therefore, these patients could potentially benefit from increased cervical cytological screening. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV), like any other virus, needs to penetrate the host cell and make use of its machinery to replicate. From there, HPV infection can be asymptomatic or lead to benign and premalignant lesions or even different types of cancer. HPV oncogenesis is due to the ability of the viral oncoproteins E6 and E7 to alter the control mechanisms for the growth and proliferation of host cell. Therefore, the use of agents with the ability to control these processes is essential in the search for effective treatments against HPV infections. Glycyrrhizinic acid (Gly), the active ingredient in liquorice, has been shown in numerous preclinical studies to have an antiviral and anticancer activity, reducing the expression of E6 and E7 and inducing apoptosis in cervical cancer cells. In addition, it also has antioxidant, anti-inflammatory, immunomodulatory or re-epithelializing properties that can be useful in HPV infections. This review includes the different antiviral and anticancer mechanisms described for Gly, as well as the clinical studies carried out that position it as a potential therapeutic strategy against HPV both through its topical application and by oral administration. [ABSTRACT FROM AUTHOR]

Background: The aim of the study is to analyze the morphological characteristics of p16INK4a/Ki-67 dual stained cells (DS) in cytology, to expand understanding of potential diagnostic value of integration of biomarkers in cytology and contribute to the existing knowledge on their utility in cervical cancer screening. Materials and Methods: In our study included a total 162 woman, who had previous abnormal Pap screening results and were enrolled in an opportunistic screening program. For these participants 162 pap /p16INK4a/Ki-67 co- tests results and 29 histopathology results were available. Results: In our study, sensitivity, specificity, PPV, NPV and accuracy of p16INK4a/Ki-67 DS of cervical smear, with abnormal morphology of stained cells to detect histologic high-grade cervical intraepithelial neoplasia (CIN2+) were 91%, 94%, 93%, 94% and 93%, respectively(p<0.01). There occur 1 error. Conclusions: Our study reveals that p16INK4a/Ki-67 DS cytology is superior in detecting CIN2+ to compare pap test, but morphologic categorization of p16INK4a/Ki-67 DS cytology is not superior over morphologic non-categorization of DS cytology in detecting high grade precancerous lesion during cervical cancer screening. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of TruScreen (TS) for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with abnormal ThinPrep cytologic test (TCT) results. Methods: 466 women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) were enrolled and underwent TS, colposcopy and biopsy examination. Results: Compared with the high-risk human papillomavirus (hrHPV) test for CIN2+, significantly higher specificity of TS, combined TS and hrHPV (69.6 and 75.0 vs 36.8% in ASCUS; 59.0 and 69.9 vs 30.1% in LSIL), significantly higher positive predictive value of combined TS and hrHPV were observed (32.7 vs 24.6% in ASCUS; 47.9 vs 35.6% in LSIL). Conclusion: TS combined with hrHPV showed better performance in diagnosing CIN2+ in ASCUS/LSIL. [ABSTRACT FROM AUTHOR]

Objective: To improve the management of mild cervical dysplasia by correcting serum folic acid as an epigenetic risk factor for disease progression. Materials and methods: 90 patients with different outcomes of dynamic follow-up of LSIL associated with one type of HPV VCR were included in the study (16, 18, 33). Group I — 43 patients with regression of the disease; Group II — 30 patients with persistence of HPV infection and group III — 17 patients with LSIL progression. The effectiveness of the differentiated approach to the management of patients in the study groups was assessed based on the results of cytology of cervical smears and immunocytochemical reaction, the level of viral load, the results of colposcopic examination, and the dynamics of serum folic acid levels. Statistical processing of the results was performed using IBM SPSS Statistics 28.0.1.1, STATISTICA 13.5.0.17 and MedCalc 20.027. Results: the prognostic significance of a number of anamnestic parameters and serum folate deficiency, the totality of which can be used as predictors of disease outcome progression, has been established; a computer program has been developed to calculate the individual risk of disease progression (IRD), which facilitates the use of the developed method for calculating progression in clinical practice. Conclusions: The proposed method with a high degree of reliability and informativeness allows predicting the progression of LSIL without violating the algorithm of current clinical recommendations, timely forming among patients a high-risk group for the development of a more severe form of the disease (HSIL) and individually determining further treatment tactics.

Aim. To determine the change of lipid levels in the cervical epithelial cells during the treatment of chronic cervicitis and low-grade squamous intraepithelial lesions (LSIL) with 0.1% activated glycyrrhizic acid. Materials and methods. The prospective cohort study included 40 patients with chronic cervicitis and 40 patients with LSIL. Cytological evaluation of cervical smears was performed according to the Bethesda system (2014). All patients received Epigen Intim Spray for 18 months. Amplification of type-specific DNA fragments of human papillomavirus (HPV) and human DNA (sampling control SC) was done using a kit of reagents to detect, type, and quantitatively determine 21 HPV types by Quantum-21 HPV PCR. Lipid extract of a cervical epithelial scraping taken before and after therapy was analyzed by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Lipids were identified using the Lipid Match R-script and by characteristic MS/MS. Correlation analysis of the lipidome of cervicovaginal fluid and SC was performed using the Spearman test, and the Mann-Whitney test was used to compare lipid levels at the two time points. Results. During the treatment of chronic cervicitis, the levels of CL lipids 16:0_16:1_18:1_18:1, HexCer-NDS d20:0/26:0, PC 16: 0_18: 1 and 16: 0_20:4 were decreasing; during the treatment of LSIL, the levels of ceramides and glucosylceramides were decreasing. Chronic cervicitis is characterized by a positive correlation of SC smear with cardiolipins, glucosylceramides, and epithelial lipids with an ether bond; LSIL showed a negative correlation with phosphatidylcholines and phosphatidylethanolamines with an ether bond. Conclusion. As a result of treatment with activated glycyrrhizic acid, the lipid spectrum of epithelial cells significantly changed, depending on the type of lesion. It is also necessary to consider SC scrapings in further studies of epithelial cell lipidome and the type of HPV-associated lesions that affects the adjustments.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSILs), but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3 months of supplementation with 600 mg of ALA on antioxidant and lipid status parameters in 100 patients with LSILs were investigated in a randomized, placebo-controlled study. The obtained results are discussed in terms of patients' initial metabolic status and diet quality (particularly nutritional intake of antioxidants). The obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted in a small but statistically significant increase in serum low density lipoprotein (LDL), and the observed effect was significantly affected by the initial lipid status of the participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment. [ABSTRACT FROM AUTHOR]

Aim. Toassess the prevalence of various types of human papillomavirus (HPV) of high carcinogenic risk (HCR) and the rate of abnormal findings of cytological examination in HPV-positive and HPV-negative women of the Kemerovo region. Materials and methods. A continuous cross-sectional study was conducted. The study included 675 women aged 21 to 65 (mean age 40.510.6 years) residing in the Kemerovo region. Patients were sampled from the cervical canal for semi-quantitative HPV-typing and cytological examination with Papanicolaou staining (PAP-test) using a liquid-based cytology method. For HPV-positive patients, an HPV typing with the quantification of 14 HCR HPV types was performed by polymerase chain reaction with real-time detection. Statistical data processing was performed using the StatSoft Statistica 6.1 software bundle. Results. The mean rate of HCR HPV detection in women of the Kemerovo region in the age group of 2165 years is 17.8% and decreases with age. HPV type 16 prevailed and was detected in 31.6% of women. In 19.2% of women, the HPV subtype 31 was diagnosed; in 18.3%, the subtype 35; in 16.7%, the subtype 33. The HPV subtypes 39, 56, and 66 were the rarest. One subtype of HCR HPV was detected in 26.7% of women, two subtypes in 6.7%, and three or more subtypes in 66.6% of women. According to the cytological examination, CIN 1, 2, and 3 rates were 3.3, 0.8, and 0.7%, respectively. HSIL (CIN 23) was detected in 1.5% of cases, LSIL (CIN 1) in 3.3%. The rate of CIN 1 in HPV(+) women was higher: 13.3% vs 1.0% in HPV(-) (2=43.197; p0.001). CIN 2 and CIN 3 were reported in HPV(+) patients only. HSIL+ was diagnosed in 7.9% of HPV(+) females (2=39.778; p0.001). Conclusion. Thus, the study results showed that the mean infection rate of HCR HPV in women of the Kemerovo region at the age of 2165 years is 17.8% and decreases with age. HPV subtype 16 is predominant; subtypes 31, 35, and 33 were less common. In HPV-positive women, abnormal findings of cytological examination were significantly more common.

Objective: To triage low-grade cervical smears (ASCUS/LSIL) by HPV 16/18 genotyping and dual staining with p16/Ki67 and to compare the sensitivity and specificity of these two triage methods for detection of high-grade cervical intraepithelial neoplasia (HGCIN). Methods: In this prospective cross-sectional study, we evaluated a total of 89 women with low-grade smears (54 ASCUS, 35 LSIL) recruited from a tertiary care hospital. All patients underwent colposcopy guided cervical biopsy. Histopathology was used as gold standard. All samples were subjected to HPV 16/18 genotyping (excluding 9) using DNA PCR and p16/Ki67 dual staining (excluding 4) using Roche® kit. We then compared the two triage methods to detect high-grade cervical lesions. Results: Overall, in all low-grade smears sensitivity, specificity and accuracy of HPV 16/18 genotyping, was found to be 66.7%, 77.1% and 76.2% respectively (p = 0.03). In low-grade smears sensitivity, specificity and accuracy of dual staining, was found to be 66.7%, 84.8% and 83.5% respectively (p = 0.01). Conclusions: Overall, in all low-grade smears the sensitivity of the two tests was comparable. However, dual staining had a higher specificity and accuracy than HPV 16/18 genotyping. It was concluded that both are effective triage methods but dual staining had a better performance than HPV 16/18 genotyping. [ABSTRACT FROM AUTHOR]

Vitamin D along with its active metabolite calcitriol and its metabolic and signaling system, known as the vitamin D endocrine system, have been widely recognized as a pivotal regulator of calcium homeostasis in addition to non-calcemic antitumoral effects in a variety of human cancers, including cervical cancer. Several studies have found an inverse relationship between the incidence of cervical neoplasia and vitamin D levels. This narrative review updates the current evidence supporting the notion that the vitamin D endocrine system has a preventive role on cervical cancer, mainly in the early phases of the disease, acting at the level of suppressing cell proliferation, promoting apoptosis, modulating inflammatory responses, and probably favoring the clearance of human papillomavirus-dependent cervical lesions. Although an optimal vitamin D status helps in the prevention and regression of low-grade squamous intraepithelial lesions of the cervix, it appears that vitamin D alone or combined with chemotherapeutic agents has little effectivity once advanced cervical cancer is established. These observations suggest that an optimal vitamin D status might exert beneficial actions in the early phases of cervical cancer by preventing its onset and progression. [ABSTRACT FROM AUTHOR]

Background: The first HPV-vaccine eligible cohorts in the Netherlands will enter the cervical screening program in 2023. However, a substantial number of young women already have had a cervical sample taken before entry into the regular screening program. This study was initiated to explore early effects of HPV vaccination on detection of cytological abnormalities in cervical samples of women younger than the screening age. Methods: Results of cervical samples were obtained from the Dutch National Pathology Databank (PALGA) and were linked to the women's HPV vaccination status from the national vaccination registry (Praeventis) (N = 42,171). Occurrence of low-grade and high-grade squamous intraepithelial lesions or worse (LSIL and HSIL+) and high-risk HPV positive tests (hrHPV) in the first cervical sample were compared between vaccinated and unvaccinated women by multivariable logistic regression analysis, corrected for age at cervical sampling and age of vaccination (12/13 years, = = 14 years). Results: For fully vaccinated women (three-or two-dose schedule), statistically significant reductions were seen for all outcomes compared to unvaccinated women (hrHPV: adjusted OR, 0.70, 95% CI, 0.63-0.79; LSIL: 0.70, 0.61-0.80; HSIL+: 0.39, 0.30-0.51). Conclusions: By linking nation-wide registries on pathology and vaccination, we show significant beneficial early effects of HPV-vaccination on LSIL, HSIL+, CIN3/AIS/carcinoma and hrHPV detection in young women upto 24 years of age who have a cervical sample taken before entry into the cervical cancer screening program. [ABSTRACT FROM AUTHOR]

In the epithelial–mesenchymal transition (EMT) process, cells lose their epithelial phenotype and gain mesenchymal features. This phenomenon was observed in the metastatic phase of neoplastic diseases, e.g., cervical cancer. There are specific markers that are expressed in the EMT. The aim of this study was to determine the localization of and associations between the immunohistochemical (IHC) expression of TWIST, SNAIL, and SLUG proteins in precancerous lesions and cervical cancer. The IHC analysis disclosed higher expressions of EMT markers in precancerous lesions and cervical cancer than in the control group. Moreover, stronger expression of TWIST, SNAIL, and SLUG was observed in cervical intraepithelial neoplasia grade 3 (CIN3) vs. CIN1, CIN3 vs. CIN2, and CIN2 vs. CIN1 cases (p < 0.05). In cervical cancer, IHC reactions demonstrated differences in TWIST, SNAIL, and SLUG expression in grade 1 (G1) vs. grade 2 (G2) (p < 0.0011; p < 0.0017; p < 0.0001, respectively) and in G1 vs. grade 3 (G3) (p < 0.0029; p < 0.0005; p < 0.0001, respectively). The results of our study clearly showed that existing differences in the expression of the tested markers in precancerous vs. cancerous lesions may be utilized in the diagnosis of cervical cancer. Further studies on bigger populations, as well as in comparison with well-known markers, may improve our outcomes. [ABSTRACT FROM AUTHOR]

Background: The persistence of the HPV infection is a risk factor in the integration of viral DNA in the host genome, leading to transforming events. The lack of therapies for HPV-persistent infections determine an unmet medical need. Methods: We enrolled forty patients with persistent HPV infections and cervical lesions and divided them into two groups. The women in the treated group received 200 mg epigallocatechin gallate (EGCG), 400 µg folic acid (FA), 1 mg vitamin B12, and 50 mg hyaluronic acid (HA) for 12 weeks. The control group received no treatment. Results: 40 patients completed the study. Fifteen out of 20 women in the control group still had an LSIL at the end of the study. One woman had a decrease in the DNA load, while six had no change and eight had an increase in DNA content. In the treatment group, 17 out of 20 women achieved a full viral clearance. These women showed no cytological or histological evidence of lesions following the treatment. Conclusions: Our data highlight the possible effect of such combination on LSIL. Therefore, the evidence reported here supports the potential to carry out further randomized placebo-controlled studies with an adequate number of patients to verify our results. [ABSTRACT FROM AUTHOR]

Objective: to identify informative markers of the progression of cervical intraepithelial lesions of low degree.Materials and methods: the dynamics of the results of the cytological study of cervical epithelium, genotyping of human papilloma viruses of high carcinogenic risk (HPV) with an assessment of the viral load, an immunocytochemical study of the expression of protein p16 (p16INK4α), serum folic acid in 90 HPV-positive patients of reproductive age was analyzed. 43 of the 90 patients (47.8%) who made up group I had regression of the disease. Group II included 30 of 90 patients (33.3%) with disease persistence - no significant changes in the results of laboratory and instrumental research methods. Group III was 17 out of 90 patients (18.9%) with disease progression. Statistical processing of the results was carried out using parametric and non-parametric analysis methods using IBM SPSS Statistics 28.0.1.1 (developed by IBM Corporation), STATISTICA 13.5.0.17 (developed by StatSoft.Inc) and MedCalc 20.027. Results: factors that significantly distinguish patients with persistence or progression of low grade cervical intraepithelial lesions from women with regression of the disease are: earlier age of sexual onset, detection of atypical changes in low grade cervical epithelium, clinically significant HPV viral load, detection of p16INK4a protein expression, serum folic acid below 3.1 ng/ml. Conclusions: deficiency of serum folic acid in HPV of positive patients should be considered as a pathogenetically significant risk factor for the implementation of infection into the clinical form of the disease, which is confirmed by its correlation with the cytological detection of LSIL, progressive increase in the copy of HPV, and p16INKα expression. The patient management strategy, which provides a personalized assessment of the risk of progression of cervical intraepithelial lesions, expands the monitoring of patients with cervical neoplasias associated with HPV.

Introduction: Low-grade squamous intraepithelial lesions (LSIL) is the primary underlying modification of the development of cervical cancer, and the most important etiological factor is the human papillomavirus. In the Republic of Moldova this diagnosis tends to progress due to an insufficiently developed screening programme. Materials and methods: retrospective and prospective data including medical records of 135 patients admitted to the Oncology Institute of the Republic of Moldova during the period 2017-2021 in which those patients diagnosed with LSIL were detected and studied. Results: Of the 135 patients studied, the prevalence of ASC-US in patients aged 17-26 years was about 18.75%. About 49.63% detected with high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 59, 66, 68. The method most chosen by patients in the diagnostic process was the ThinPrepPap test, about 49% of patients. Conclusions: The incidence of cervical cancer is increasing in developing countries where cervical screening programmes are not yet well organized. The human papillomavirus (HPV) has an affinity for epithelial tissue, especially at sites with lesions, and infection itself depends on changes in the basal layer of the epithelium. [ABSTRACT FROM AUTHOR]

We aim to describe the relationship between the immunohistochemical expression patterns of HPV E4 markers and the presence of HPV major capsid protein (L1) in cervical tissues obtained by biopsy of patients with abnormal liquid-based cytology (LBC) results, HR HPV infections, or clinically suspicious cervix. A novel HPV-encoded marker, SILgrade-E4 (XR-E4-1), and an HPV (clone K1H8) antibody were used to demonstrate the expression in terminally differentiated epithelial cells with a productive HPV infection in the material. A semiquantitative analysis was performed based on light microscope images. The level of E4 protein decreased with the disease severity. Patients with LSIL-CIN 1 and HSIL-CIN 2 diagnoses had significantly lower levels of HPV major capsid protein (L1) than those without confirmed cervical lesions. Our analysis confirms a higher incidence of L1 in patients with molecularly diagnosed HPV infections and excluded lesions of LSIL-CIN 1 and HSIL-CIN 2. Further studies on the novel biomarkers might help assess the chances of the remission of lesions such as LSIL-CIN 1 and HSIL-CIN 2. Higher levels of E4 protein and L1 may confirm a greater probability of the remission of lesions and incidental infections. In the cytological verification or HPV-dependent screening model, testing for E4 protein and L1 expression may indicate a group with a lower risk of progression of histopathologically diagnosed lesions. [ABSTRACT FROM AUTHOR]

Objective: At the present time, cervical cancer remains the fourth most prevalent cancer among women worldwide. Most cervical cancer cases are attributed to high-risk human papillomavirus (HPV) infection. Because the natural history of cervical cancer takes decades, the disease could be prevented if premalignant conditions are identified and appropriately managed. The aim of this study is to identify the prevalence of precancerous lesions among non-vaccinated women attending the national tertiary care hospital in Kazakhstan. Methods: This was a retrospective study of the cervical cancer screening database (2018) from the national tertiary care hospital in Kazakhstan. Records of 6682 patients, who had cervical cytology tests by Papanicolaou (Pap test), were analyzed. Out of the revised cases, 249 patients had abnormal cervical cytology reports. The Pap test was performed using liquid-based cytology (LBC). The data were analyzed using the statistical software STATA 16. A p-value of less than 0.05 was considered statistically significant. Results: In this retrospective analysis of 6682 patients' records, we found 3.73% (249 patients) out of all Pap tests performed in 2018 were abnormal. The prevalence of high-grade squamous intraepithelial lesion (HSIL) was high at 19.28%, and the proportion of atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells (ASCs-H) was 18.47%, while low-grade squamous intraepithelial lesion (LSIL) were identified in 62.25% of the cases. Almost 25% of the women included in the study had concurrent lower and upper genital tract infections. Conclusion: Although the overall rate of abnormal Pap test results was not high, the study shows the elevated prevalence of HSIL. It calls the attention of local policymakers and gynecology specialists and requires immediate actions to improve the prophylactic measures to decrease morbidity and mortality from cervical cancer in Kazakhstan. [ABSTRACT FROM AUTHOR]

Simple Summary: Roughly, 5% of all women undergoing screening for cervical cancer suffer from cervical intraepithelial neoplasia (CIN). Persistent and high grade CIN are usually treated by conization. Conization is associated to several long-term complications such as preterm deliveries. Therefore, non-surgical treatment approaches to CIN are urgently needed. Up to now only retrospective data were available for the topical treatment with trichloroacetic acid (TCA). This is the first prospective trial showing high efficacy of TCA in the treatment of CIN. In the future, TCA may represent an effective and feasible non-surgical treatment approach for CIN. Data on non-surgical treatment approaching persistent cervical intraepithelial neoplasia (CIN) are scarce. Retrospective analysis suggest high efficacy of topical treatment with trichloroacetic acid (TCA). This prospective phase II study set out to investigate the efficacy of a single application of 85% TCA in the treatment of CIN I/II. Patients with CIN I/II were treated a single time with 85% TCA. After three and six months colposcopic, histologic, and HPV evaluation was performed. The primary endpoint was treatment efficacy defined as complete histologic remission six months after treatment. The secondary endpoint was HPV clearance six months after treatment. A total of 102 patients with CIN I/II were included into this trial. Complete histologic remission rates were 75.5% and 78.4% three and six months after TCA treatment, respectively. Clearance rates of HPV 16, 18 and other high risk types were 76.5%, 91.7%, 68.7% after six months, respectively. Side effects of TCA were mild and lasted usually less than 30 min. This is the first prospective trial reporting high histologic complete remission rates in patients with CIN I/II after a single 85% TCA treatment. In the future, TCA may represent an effective and feasible non-surgical treatment approach for CIN. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study is to compare the clinical data and colposcopy-directed biopsy (CDB) results of atypical squamous cell of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cytology among high risk human papilloma virus (hrHPV) positive women. Materials and Methods: A total of 359 hrHPV-positive patients with ASC-US and LSIL cytology, between 20-67 years of age were included in the study. Participants' age, education status, smoking status, colposcopy results, and number of CDBs were assessed and clinical data compared with histopathologic evaluation of biopsies statistically. Results: There were no statistically significant differences in terms of age, marital status, education status and smoking status of hrHPV+ASC-US and hrHPV + LSIL groups. Both groups were compared in terms of histopathologic results of CDBs and no statistically significant difference was observed between the groups. The number of CDB material and frequency of endocervical curettage were significantly higher in hrHPV + LSIL than hrHPV + ASC-US patients. There was no statistically significant difference between the two groups in terms of advanced treatment need. Control cytology performed during follow-up of both ASC-US and LSIL groups were resulted as benign. Conclusion: The approach to ASCUS and LSIL is similarly important in HPV positivity. Since our follow up period includes a sort period of 1 year, further studies need to be carried out in order to demonstrate longer teim outcomes. [ABSTRACT FROM AUTHOR]

Background: High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell cancer (ASCC) precursors. Although it is superior to other diagnostic methods, particularly cytology, the visual identification of areas suspected of having high-grade squamous intraepithelial lesions remains difficult. Convolutional neural networks (CNNs) have shown great potential for assessing endoscopic images. The aim of the present study was to develop a CNN-based system for automatic detection and differentiation of HSIL versus LSIL in HRA images. Methods: A CNN was developed based on 78 HRA exams from a total of 71 patients who underwent HRA at a single high-volume center (GH Paris Saint-Joseph, Paris, France) between January 2021 and January 2022. A total of 5026 images were included, 1517 images containing HSIL and 3509 LSIL. A training dataset comprising 90% of the total pool of images was defined for the development of the network. The performance of the CNN was evaluated using an independent testing dataset comprising the remaining 10%. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve (AUC) were calculated. Results: The algorithm was optimized for the automatic detection of HSIL and its differentiation from LSIL. Our model had an overall accuracy of 90.3%. The CNN had sensitivity, specificity, positive and negative predictive values of 91.4%, 89.7%, 80.9%, and 95.6%, respectively. The area under the curve was 0.97. Conclusions: The CNN architecture for application to HRA accurately detected precursors of squamous anal cancer. Further development and implementation of these tools in clinical practice may significantly modify the management of these patients. [ABSTRACT FROM AUTHOR]

Purpose: We assessed human papillomavirus (HPV) genotype-based risk stratification and the efficacy of cytology testing for cervical cancer screening in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL)., Materials and Methods: Between 2010 and 2021, we monitored 1,237 HPV-positive women with ASCUS/LSIL every 6 months for up to 60 months. HPV infections were categorized as persistent (HPV positivity consistently observed post-enrollment), negative (HPV negativity consistently observed post-enrollment), or non-persistent (neither consistently positive nor negative). HPV genotypes were grouped into high-risk (Hr) groups 1 (types 16, 18, 31, 33, 45, 52, and 58) and 2 (types 35, 39, 51, 56, 59, 66, and 68) and a low-risk group. Hr1 was subdivided into types a) 16 and 18; b) 31, 33, and 45; and c) 52 and 58. Cox regression and machine learning (ML) algorithms were used to analyze progression rates., Results: Among 1,273 participants, 17.6% with persistent HPV infections experienced disease progression versus no progression in the HPV-negative group (p<0.001). Cox analysis revealed the highest hazard ratios (HRs) for Hr1-a (11.6, p<0.001), followed by Hr1-b (9.26, p<0.001) and Hr1-c (7.21, p<0.001). HRs peaked at 12-24 months, with Hr1-a maintaining significance at 24-36 months (10.7, p=0.034). ML analysis identified the final cytology change pattern as the most significant factor, with 14-15 months the optimal time for detecting progression from the first examination., Conclusion: In ASCUS/LSIL cases, follow-up strategies should be based on HPV risk types. Annual follow-up was the most effective monitoring for detecting progression/regression.

Abstract Background Anal squamous intraepithelial lesions (ASIL), strongly related to human papilloma virus (HPV) infection, is more prevalent among men who have sex with men (MSM). However, no such data are available for Pakistan yet, and neither HPV vaccination nor anal-cytology screening is implemented in Pakistan. The purpose of this first ever study was to assess the prevalence of HPV-related anal cytological abnormalities among MSM and transgender women living with and without HIV infection in Pakistan. Methods We conducted a cross-sectional study from March 2016 to November 2017 at sexual health centers run by the Perwaaz Trust and the National AIDS Control Program in Karachi. The study enrolled MSM and transgender women aged greater-than-and-equal-to-18-years who reported anal sex in the preceding 6 months. We collected two anal samples for liquid-based cytology and HPV type testing by PCR, and socio-demographic and behavioral data were collected through face-to face interviews. ASIL and its associations with biological and behavioral risk factors were analyzed through Cox regression for prevalence ratios (PR) and corresponding 95% confidence intervals (CIs). Results Out of 271 qualifying participants, 79% were MSM and 21% transgender women. The mean age was 28.8 (± 8) years. Almost 35% (93/271) of the study population had ASIL detected, ASIL was significantly more common among participants living with HIV than in HIV negative ((50/118) 42.4%; vs. (43/153) 28.1%) (p ≤ 0.001). Among ASIL, 66% (61/93) had low-grade squamous intraepithelial lesions (LSIL), and 3.6% (3/93) had high-grade squamous intraepithelial lesions (HSIL). The overall, HPV16 positivity was 35.5% (33/93) among all abnormal anal lesions and all 3 HSIL were HPV16 positive, however, HPV16 positivity could show its association with ASIL detection in univariate model only (PRcrude: 2.11(1.39–3.18)). Moreover, any HR-HPV type (PR 3.04; 95% CI 1.75–5.26), concurrent sexually transmitted infection (STI) (2.13; (1.28–3.55)) and HIV + /HPV + coinfection (1.75; (1.07–2.88)) remained independently associated with ASIL in the multivariate model. Conclusions Abnormal anal cytology among MSM and transgender is prevalent enough to consider optimal screening regimens. Further studies are required to see if periodic anal cytology can be made part of HIV care and treatment programs among MSM in Pakistan.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSILs), but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3 months of supplementation with 600 mg of ALA on antioxidant and lipid status parameters in 100 patients with LSILs were investigated in a randomized, placebo-controlled study. The obtained results are discussed in terms of patients’ initial metabolic status and diet quality (particularly nutritional intake of antioxidants). The obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted in a small but statistically significant increase in serum low density lipoprotein (LDL), and the observed effect was significantly affected by the initial lipid status of the participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

This article presents the results of our own experience of topical use of the Prodexin antiseptic that is contained an octenidine dihydrochloride molecule as a monotherapy for ASC-US and LSIL cervical pathology (identified with in fluid cytology) associated with human papillomavirus in smoking women. Study objective: To study the efficacy of topical application of the octenidine dihydrochloride molecule in the Prodexin vaginal suppositories in the treatment of smoking women with ASC-US and LSIL. Materials and methods. The study involved 45 female smokers with identified ASC-US or LSIL. The complex of examination included: Pap test based on liquid cytology, testing for human papillomavirus 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 types in a quantitative format, screening for the causes of vaginitis, extended colposcopy to exclude cervical intraepithelial neoplasia II+. Prodexin suppositories were used according to a 3-month treatment regimen (20 suppositories daily, and then 10 suppositories in two consecutive cycles). Results. Clinical and laboratory assessment of the therapy effectiveness has convincingly shown its positive effect on the vagina and cervix. Treatment with the Prodexin antiseptic associated with microbiota normalization, colposcopic picture improvement and changes in the Pap smear to NILM I or II. Regress to NILM was recorded in 20 (86.9%) patients with ASC-US and in 15 (68.8%) women with LSIL. Conclusions. Prodexin allows to avoid a worsening of the situation and prevent the changes progression in HSIL. Proposed treatment had no side effects, was convenient to use and did not require additional visits to doctor during therapy. The control over the human papillomavirus and study of the viral load has been postponed for 6–12 months from the beginning of the examination, that will be the second stage of work.

Aim. To conduct a retrospective analysis and evaluate the morphological methods for HPV-related intraepithelial lesions detection in women of reproductive age. Materials and methods. The data of cytological diagnosis, as well as the results of histological reports were analyzed for the period from 2018 to 2019. A comparative analysis was performed in 415 patients with HPV-related intraepithelial lesions, who applied to the scientific and polyclinic department of the Kulakov National Research Medical Center at the age of 19 to 45 years. Morphological examination was carried out by specialists of the 1st pathology department of the Center. Results. According to the results of a comparative analysis of cytological and histological conclusions, 3 groups were formed: 1 the group of coincidence (agree) of cytological and histological conclusions; 2 group of minor discrepancies (minor under/ over) between cytological and histological finding; 3 group of major discrepancies (major under/ over) between cytological and histological findings. Cytological and histological compliance was achieved in 194 (46.74%) patients. The total number of minor nonconformities was 192 (46%) cases. The total number of significant discrepancies between cytological and histological findings was 29 (6.9%) patients: 20 (4.8%) cases were found in the group NILM, hr. cervicitis HSIL and 9 (2.1%) cases in the group HSIL hr. cervicitis according to the results of histological examination. Conclusion. Cervical screening reduces the risk of breast cancer due to cytological examination of the cervix, but histological examination is crucial in making a correct diagnosis, since its result determines the choice of treatment method. The comparative analysis showed that in all groups there were cases of hypo- and hyperdiagnostics during cytological examination although the major discrepancies which can change treatment algorithm, were found only in 6.8% cases.

Vitamin D along with its active metabolite calcitriol and its metabolic and signaling system, known as the vitamin D endocrine system, have been widely recognized as a pivotal regulator of calcium homeostasis in addition to non-calcemic antitumoral effects in a variety of human cancers, including cervical cancer. Several studies have found an inverse relationship between the incidence of cervical neoplasia and vitamin D levels. This narrative review updates the current evidence supporting the notion that the vitamin D endocrine system has a preventive role on cervical cancer, mainly in the early phases of the disease, acting at the level of suppressing cell proliferation, promoting apoptosis, modulating inflammatory responses, and probably favoring the clearance of human papillomavirus-dependent cervical lesions. Although an optimal vitamin D status helps in the prevention and regression of low-grade squamous intraepithelial lesions of the cervix, it appears that vitamin D alone or combined with chemotherapeutic agents has little effectivity once advanced cervical cancer is established. These observations suggest that an optimal vitamin D status might exert beneficial actions in the early phases of cervical cancer by preventing its onset and progression.

Human papillomavirus (HPV) infection caused a morphological change known as Low-grade squamous intraepithelial lesion (LSIL). Certain type of HPV infection could become persistent and progress to High-grade squamous intraepithelial lesion (HSIL), which are high risk of becoming invasive cancer, Squamous cell carcinoma (SCC). Immunohistochemical staining with p16 known as the marker on cervical lesion caused by HPV infection, p16 strongly expressed on HSIL and SCC, but very weak to none on LSIL or HPV negative. Programmed Death Ligand 1 (PDL-1) pathway has an important role in decreasing T cell response and promoting T cell tolerance on chronic viral infection. Analyzing correlation between PDL-1 and p16 expressions with LSIL, HSIL and SCC of the cervix. Analytical observational conducted on paraffin block samples of the LSIL, HSIL and SCC of the cervix, at the Anatomical Pathology laboratory, Dr. Soetomo Academic General Hospital, Surabaya. Immunohistochemical staining is performed to detect expression of PDL-1 and p16. The result was statistically analyzed using Chi-Square correlation test. There are marked positive correlation between P16 and PDL-1 with LSIL, HSIL, SCC (p<0.05) with positive correlative coefficient of 0.647. There is a marked positive correlation between P16 and PDL-1 with LSIL, HSIL, SCC. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cytology has limited sensitivity to detect cervical pre-cancerous lesions. High-risk human papillomavirus (hr-HPV) DNA testing has high sensitivity but its specificity is limited. This study was done to assess the utility of p16INK4a/ki-67 dual stained cytology in improving the predictive value for high-grade cervical (CIN2+) lesions. Aim/Objective: To assess the significance of P16/Ki-67 immunocytochemistry in improving the predictive value for high-grade cervical intraepithelial (≥CIN 2+) lesions on Pap smear. Material and Methods: This was a prospective diagnostic study that included 93 patients with ASC-US/LSIL/ASC-H and HSIL on thin prep cervical smears and who also underwent hr-HPV DNA test and colposcopy-guided biopsy. Biopsy was the gold standard against which the performance of P16INK4a/Ki-67 and hr-HPV results were compared. Results: In women of all ages, sensitivity of (96.8%) hr-HPV test and p16/Ki-67 dual immunocytochemistry (≥1 positive cell) were similar and negative predictive value (NPV) was (97.1% vs. 97.9%) but the latter test showed better specificity (69.4% vs. 53.2%) and positive predictive value (PPV, 61.2% vs. 50.8%) for ≥CIN 2 lesions. A higher cut off of at least 10 positive cells gives a higher specificity and PPV, with slightly decreased sensitivity and NPV. Conclusion: Because high-risk HPV test has a high sensitivity and NPV, whereas P16/Ki-67 dual immunocytochemistry (≥10 positive cells) has a high specificity and PPV, the latter can be recommended as an ancillary test in hr-HPV-positive women to reduce the number of women going for colposcopy and biopsies.

Objective: analyze the validity of destructive treatments for cervical diseases in clinical practice.Materials and methods: analyzed archival medical documentation (medical records of an inpatient patient, form 003/y) of 258 patients who underwent surgical treatment of cervical diseases in 2017 – 2018. Statistical data were calculated on a personal computer using the Microsoft Excel 2011 for Mac program and the «Statistica» statistical program.Results: an analysis of medical documentation revealed that a complete set of diagnostic methods, regulated by the clinical recommendations “Benign and precancerous cervical diseases from the perspective of cancer prevention” (2017), including HPV genotyping, was carried out in 28.7 % women. Before surgical treatment, a cytological examination of the cervix was carried out in 89.5 % cases, HPV-test — 31.4 % patients. As a result of the comparison of 258 histological and pre-operative clinical diagnoses, overdiagnosis of low- and high-grade cervical lesions (LSIL and HSIL) was noted in 16 (23.2 %) patients who did not have a history of childbirth and 42 (22.0 %) women who had previously given birth, which determined the use of destructive treatments without indications in 58 (22.5%) cases. An underestimation of the severity of cervical damage among unborn patients was found in 9 (13.0 %) patients, as well as in 40 (21.2 %) women with a history of childbirth.Conclusions: overdiagnosis of the degree of intraepithelial cervical lesions entails the unreasonable use of destructive methods of treatment in young unborn women who violate the anatomic-functional integrity of the cervix and the architectonics of the cervical canal.

Objetivo: analisar os resultados do rastreamento de LSIL e HSIL no período de julho de 2012 a julho de 2015. Materiais e Métodos: estudo descritivo com base em dados secundários do SISCOLO. Resultados: foram realizados, no período de junho de 2012 a julho de 2015, 2.451.607 exames citopatológicos em Minas Gerais, sendo, em 2012, 743.276; 2013, 1.099.876 e 2014, 608.455 em mulheres de 10 a mais de 64 anos, em que se observa um déficit no levantamento de dados. As principais cidades em que ocorreu o maior número de casos positivos para LSIL e HSIL foram Belo Horizonte, Juiz de Fora, Montes Claros e Uberlândia. Em ambas as lesões, Belo Horizonte é a que possui a maior quantidade de casos positivos. Conclusão: há uma faixa etária em comum, 25 a 34 anos, com alto acometimento de LSIL e HSIL.

Abstract The process from high-risk human papillomavirus (HR-HPV) infection to cervical cancer is a continuous and long-term process, but the pathogenesis of the whole process is not completely clear. Here, 59 Chinese women were engaged in this study, and divided into five groups: normal healthy group, HR-HPV infections group, low-grade intraepithelial neoplasia (LSIL) group, high-SIL(HSIL) group, and cervical cancer group. With the occurrence of HR-HPV infection and the development of cervical lesions, the diversity of vaginal microbiota species was increased, and the relative abundance of Lactobacillus (L.), the dominant bacteria in maintaining vaginal microecological balance, was decreased gradually. In contrast, the abundance of Actinobacteria in the four disease groups was significantly higher than that in normal group. Furthermore L. iners may be related to the serious progression of cervical cancer. After analyzing the whole process, we found that Gardnerella(G.), Atopobium(A.) and Dialister(D.) have important effects on both persistent HR-HPV infection and the pathogenesis of cervical cancer. In addition, PICRUSt2 and KEGG results showed that the KEGG pathways enriched by the predicted genes of vaginal microbiota in cancer group included metabolic diseases, endocrine system and immune systems when compared with that in normal group. These findings may provide insights into the pathogenesis of cervical cancer, and help to improve the early detection and prevention of cervical precancerous lesions.

Background: ">Cervical cancer in India accounts for one-fifth of the global burden. Well-defined precancerous stages help early detection of the disease. Apart from human papillomavirus, the risk factors include age, education, occupation, early age at marriage and first delivery, abortions, and multiple sexual partners. Prevalence and risk factors for cervical squamous intraepithelial lesions (SIL) among women by Pap smear screening in south India were analyzed through a cross-sectional study.Methods: ">Women from rural and urban area were motivated by local accredited social health activists to attend pre-fixed Pap smear clinics in government hospitals. Pap smears collected in these clinics were taken to the Regional Cancer Centre, Thiruvananthapuram, processed, and cytology reports were prepared. Multiple logistic regression analysis was used to identify risk factors for SIL and high-grade SIL (HSIL).Results: ">The number of SIL was 67 out of 10,580 and HSIL was 39. Having higher education (Odds Ratio, OR:0.05(95% Confidence Interval, CI: 0.01-0.2), being married but living single (OR : 5.3, 95%CI:2.4-11.5), Having >2 abortions (OR:21, 95% CI:4.5-24), having younger age at delivery (OR : 0.1, 95% CI:0.01-0.3) and having unhealthy cervix (OR: 16.4, 95% CI:6.2-42.7) were the factors found to be the associated risk factors in multiple regression analysis.Conclusion: ">Pap smear screening can be focused on women with risk factors such as low education, married but living single, having >2 abortions, younger age at delivery, and unhealthy cervix on per speculum examination. [ABSTRACT FROM AUTHOR]