BACKGROUND: Cytological screening remains a high-impact practice, particularly in low-resource settings, for preventing cervical cancer. The examination of screening practices over time and the prevalence of epithelial abnormalities have not been investigated in longitudinal studies in one of the largest countries in the Middle East and Africa.
METHODS: Routine healthcare data, between March 1981 and December 2022, were extracted from the database of the Early Cancer Detection Unit in a tertiary referral university hospital in the Greater Cairo Region, Egypt. Cervical smears were obtained using a standardized technique and sent to the cytopathology laboratory for conventional cytology examination by expert pathologists. The anonymous data were analyzed to determine the temporal trend of the number of women screened each year and the prevalence of epithelial abnormalities.
RESULTS: Data included the results of satisfactory smears from 95120 women. The mean age (SD) of the women at the time of screening was 38.5 (10.5). None of the included women received an HPV vaccine. Abnormal epithelial cells were reported in 5174 women (5.44%). Of these epithelial abnormalities, the majority were low-grade squamous intraepithelial lesions in 4144 women (4.36%). Other abnormalities included atypical squamous cells in 378 women (0.40%), high-grade squamous intraepithelial lesions in 226 women (0.24%), atypical glandular cells not otherwise specified in 184 women (0.19%), adenocarcinoma in 165 women (0.17%), squamous cell carcinoma in 70 women (0.07%), and atypical glandular cells favoring neoplasms in 7 women (0.01%). Women who were at an early age at first intercourse, those who opted for routine cervical cytology screening, and those who were older at screening were more likely to have epithelial abnormalities. The yearly number of screened women was positively associated with the detection of low-grade squamous intraepithelial lesions (correlation coefficient [95% CI] = 0.84 [0.72, 0.91]) and negatively associated with the detection of squamous cell carcinoma (correlation coefficient [95% CI] = -0.55 [-0.73, -0.29]).
CONCLUSIONS: The small number of annually screened Egyptian women and the temporal trend in epithelial abnormalities critically demonstrate the need for establishing and scaling up a structured population-based program to achieve the goal of eliminating cervical cancer.

UNASSIGNED: Although several studies have been achieved on the frequency of the HPV types among women with cervical cancer in Iran, HPV-positive samples were in some cases directed to specific-primer genotyping of HPV 16 and 18. Therefore, the other HPV types are underestimated. Several studies have also reported a greater prevalence of HPV 16 in cervical cancer in Iran than in the world. To clarify these subjects, the distribution of HPV types in women referred for colposcopy in Tehran was investigated.
UNASSIGNED: In this cross-sectional study, a total of 148 cervical samples from women with normal, atypical squamous cells of undetermined significance, cervical intraepithelial neoplasia I-III, and invasive cervical cancer histopathology were included. HPV was detected by PCR assay and all HPV-positive specimens were subjected to direct nucleotide sequencing.
UNASSIGNED: Our results demonstrated that the total prevalence of HPV was 92.5%. The five most common HPV types were HPV 16 (49.3%), 18 (14.8%), 6 (7.4%), 31 (4.1%), and 11 (2.7%). About the histopathological stage, HPV 16 and 18 were dominant in all studied groups. In cervical cancer, HPV 16 and 18 were detected in 60% and 20% of cases, respectively.
UNASSIGNED: HPV 16 and 18 were the most common in cervical cancer in Iran.

UNASSIGNED: To probe cervical cancer screening practices in local women positive for human immunodeficiency virus, and to determine the cervical cytological changes in them.
METHODS: The serial cross-sectional study was conducted at the Jinnah Hospital and Services Hospital, Lahore, Pakistan, from April 2019 to October 2020, and comprised female patients aged 18-45 years who were positive for human immunodeficiency virus or acquired immunodeficiency syndrome and were registered with the relevant programme being run by the provincial government in Punjab. Blood samples of all the patients were collected for the determination of human immunodeficiency virus viral load and cluster of differentiation 4+ count. Cervical smears were taken for cytopathological analysis, while the swabs were analysed for culture sensitivity. The same individuals were subjected to the same testing one year later, and the status of the disease and clinical stability or disease progression was explored. Data was analysed using SPSS 25.
RESULTS: There were 150 women with mean age 32.08±7.13 years (range: 21-45 years). Age at marriage/sexual activity was 17.33±4.73 years in 15(10%) subjects. Cytological examination showed atypical squamous cells of undetermined significance in 6(4%) of the cases whereas 3(2%) cases showed atypical squamous cells, which cannot rule out high grade squamous intraepithelial lesion on cytology, while the rest were classified as negative for intraepithelial lesion or malignancy. Cervical microbial changes revealed methicillin-resistant staphylococcus aureus infection in 9(6%) cases, extended-spectrum beta-lactamase in 15(10%) cases, whereas fungal infection and trichomonas vaginalis infection were found in 30(20%) smears. There was a significant association between cluster of differentiation 4+ cell count and stability of high-risk patients (p<0.001). After one year, 84(56%) patients remained clinically stable, while 51(34%) developed some chronic illness. There was a significant association between cluster of differentiation 4+ cell count <200/mm3 and the risk of developing a chronic illness (p<0.001).
CONCLUSIONS: There was a dire need to educate healthcare workers to offer regular cervical screening to patients with high-risk sexually-transmitted infections to prevent them from the morbidity and mortality related to cervical cancer.

Human papillomavirus (HPV) is the most common sexually transmitted pathogen that causes anogenital disease. Cervical screening by cytology and HPV testing (co-testing) are important in prevention of cervical cancer. The Bethesda System category of atypical squamous cells (ASC) is used when a neoplastic process cannot be confidently identified. In such cases, the differential diagnosis is broad and includes benign conditions. Monitoring of ASC/SIL ratio is a commonly used laboratory quality assurance measure to prevent over- or under-use of this category. High risk human papillomavirus (hr-HPV) has been used in conjunction with the ASC/SIL ratio in determining whether a particular pathologist is over/under-using the indefinite category. However, the laboratory overall sample population prevalence rate of hr-HPV subtypes has not been previously examined for association with the ASC rate. In this study, the relationships between ASC/SIL ratio and hr-HPV prevalence rate and hr-HPV subtypes (16/18 and non-16/18) to the laboratory ASC prevalence were studied. The results demonstrate that HPV non-16/18 is the main subtype which is associated with ASC-US category. A large proportion of non-16/18 HPV-related cases are seen in young patients, which largely abates by the by fourth decade. In addition, there are differences in the ASC/SIL ratio for HPV 16/18 and non-16/18 types. The overall ASC/SIL ratio is an average of the ASC/SIL rate for the non-16/18 population and the HPV 16/18 population. Instead of basing the laboratory and practitioners\' quality indicator solely on ASC/SIL ratio, the overall prevalence of HPV and its subtype ratio should also be reported as they are more reflective of laboratory performance.

UNASSIGNED: The importance of Cervicovaginal Microbiota in protecting against infections (such as HPV) is already well established, namely through Lactobacillus spp., as well as the mechanism through which HPV leads to Cervical Neoplasia. However, it is not possible to classify HPV as a complete carcinogen. Thus, the importance of exploring Cervicovaginal dysbiosis with the intention of deciphering this interaction with HPV, takes on greater relevance. The main objectives of this study were: 1) Comparison of the MCV composition of women with or without HPV and women with ASCUS or LSIL; 2) Characterization of cytokines present in the vaginal microenvironment; 3) Evaluation of the blood count ratios as prognostic systemic inflammatory biomarkers; 4) Correlation between MCV, HPV serotypes and cytokines.
UNASSIGNED: This was a retrospective, observational, multicenter, cross-sectional study. CVM analysis was performed by isolation RNA and sequencing on a NGS platform. Cytokine concentrations of CVM were obtained through Multiplex platform. Statistical analysis was performed in SPSS v 26.0. An α of 0.05 was considered statistically significant.
UNASSIGNED: Highlighting the core of the study, CVM types of CST I and CST IV were found to influence the emergence of cervical lesions. Neutrophil-to-Lymphocyte ratio was found to impact the prognosis of ASCUS. Within CVM, Lactobacillus prevent the growth of other CST IV species, while the latter express symbiotic relationships with each other and show affinity for specific HPV serotypes. At last, RANTES chemokine is significantly elevated in cervicovaginal infections.
UNASSIGNED: The importance of using vaginal cytokine profiles and CVM is highlighted in the hypothesis of prevention of Cervical Neoplasia development, as well as in its use as a prognostic biomarker. Taken together, these insights are one step closer to personalized medicine.

OBJECTIVE: Currently, traditional cervical cancer screening methods, such as high-risk human papillomavirus testing and liquid based cytology (LBC), still possess limitations. This study aims to identify new diagnostic biomarkers to achieve the goal of \"precision screening\" via exploring the clinical value of DNA methylation [ΔCtP: paired box gene 1 (PAX1)and ΔCtJ: junctional adhesion molecule 3 (JAM3)] detection in cervical exfoliated cells for the diagnosis of high-grade cervical lesions.
METHODS: A total of 136 patients who underwent gynecological examinations in the vaginal room of the Department of Gynecology at the Third Xiangya Hospital of Central South University from June 2021 to June 2022 were retrospectively studied. Among them, 122 patients had non-high-grade cervical lesions, and 14 patients had high-grade cervical lesions. The variables included general information (age, body mass index, and menopause status), LBC, high-risk human papillomavirus, cervical tissue pathology, vaginal examination results, and the ΔCt values of JAM3 and PAX1 gene methylation. Logistic regression analysis was used to identify the factors affecting the diagnosis of high-grade cervical lesions, followed by correlation analysis and construction of a conditional inference tree model.
RESULTS: Logistic regression analysis showed that the methylation ΔCt values of PAX1 and JAM3 genes and LBC detection results were statistically significant between the high-grade cervical lesions group and the non-high-grade cervical lesions group (all P<0.05). Correlation analysis revealed a negative correlation between cervical pathological changes and ΔCtP (r=-0.36, P<0.001), ΔCtJ (r=-0.448, P<0.001), LBC (r=-0.305, P<0.001), or bacterial diversity (r=-0.183, P=0.037). The conditional inference tree showed that when ΔCtJ>10.13, all of patients had non-high-grade cervical lesions, while ΔCtP>6.22, the number of non-high-grade lesions accounted for 97.5% (117/120), and high-grade lesions accounted for only 2.5% (3/120). When ΔCtJ>8.61 and LBC were atypical squamous cell of undetermined significance or negative for intraepithelial lesions or malignancy (NILM), 105 (99.1%) patients were non-high-grade cervical lesions, only 1 (0.9%) patient was high-grade lesion. When the results of LBC were high-grade lesions, only 9 patients\' histopathological examination was the high-grade lesions and 3 non-high-grade lesions. When LBC indicated low-grade lesions, atypical squamous cell of undetermined significance, no intraepithelial lesions, and ΔCtP>6.22, 117 (97.5%) of patients\' histopathological examination was the non-high-grade lesions.
CONCLUSIONS: The JAM3/PAX1 gene methylation test can be used independently for the stratified diagnosis of high-grade/non-high-grade cervical lesions in women with high-risk human papillomavirus infection, independent of the cytological results of cervical excision. The JAM3/PAX1 gene methylation test can also be used in combination with LBC to make up for the shortcomings of low sensitivity of LBC. In addition, the application of methylation kit in large-scale cervical cancer screening in the future will be good to the detection of more patients with high-grade cervical lesions, and achieve early screening and early treatment for cervical lesions/cancer.
目的: 传统的宫颈癌筛查手段——高危型人乳头瘤病毒(high-risk human papillomavirus，hrHPV)和宫颈脱落细胞学检测存在局限性。本研究通过检测宫颈脱落细胞中连接黏附分子3(junctional adhesion molecule 3，JAM3)/配对盒基因1(paired box gene 1，PAX1)高甲基化水平，并将其与液基薄层细胞学(liquid based cytology，LBC)进行比较，评价JAM3/PAX1甲基化对于宫颈高级别病变的诊断能力，以探索新的宫颈高级别病变的诊断模式，实现宫颈高级别病变“精准筛查”的目的。方法: 回顾性收集2021年6月至2022年6月在中南大学湘雅三医院妇科阴道镜门诊接受检查的患者共136例，包括宫颈非高级别病变122例，高级别病变14例。研究的变量包括：基本临床信息(年龄、体重指数、是否绝经)、LBC、hrHPV、宫颈组织病理、阴道微生态结果、阴道镜结果(宫颈转化区类型)、JAM3(ΔCtJ)和PAX1(ΔCtP)基因甲基化的ΔCt值。首先通过logistic回归分析筛选影响宫颈高级别病变的影响因素，并进行相关性分析，然后用差异有统计学意义的变量构建条件推断树模型。结果: Logistic回归分析提示高级别宫颈病变组与非高级别宫颈病变组的PAX1与JAM3基因甲基化ΔCt值以及LBC检测结果差异均有统计学意义(均P<0.05)。相关性分析发现，宫颈病理结果与ΔCtP(r=-0.360，P<0.001)、ΔCtJ(r=-0.448，P<0.001)、LBC(r=-0.305，P<0.001)、菌群多样性(r=-0.183，P=0.037)呈负相关。条件推断树显示：当ΔCtJ>10.13时，全部为宫颈非高级别病变的患者；当ΔCtP>6.22时，非高级别病变的患者有117例，占97.5%，高级别病变者仅3例，占2.5%。ΔCtJ>8.61且LBC为不明确的非鳞状上皮细胞(atypical squamous cell of undetermined significance，ASC-US)或未见上皮内病变细胞时，105例(99.1%)为宫颈非高级别病变的患者，仅1例(0.9%)检出为高级别病变；当LBC结果为高级别病变时，仅9例患者检出高级别病变，3例检出非高级别病变；而当LBC提示低级别病变、ASC-US、未见上皮内病变细胞，且ΔCtP>6.22时，有117例(97.5%)的患者检出非高级别病变。结论: 在人乳头瘤病毒感染妇女中，JAM3/PAX1双基因甲基化检测可独立应用于宫颈高级别病变/非高级别病变的分层诊断，且不依赖于宫颈脱落细胞学检测结果；亦可与LBC联合使用以弥补LBC敏感度低的缺点。此外，未来将甲基化试剂盒应用于大规模宫颈癌筛查，有利于发现更多宫颈高级别病变患者，并达到早筛、早治宫颈病变/癌的目的。.

BACKGROUND: Liquid-based cytology (LBC) has replaced conventional smear (CS) in the world. In this study, through a series with a large number of cases, we aimed to make a comparison and general evaluation in all groups, primarily epithelial abnormalities, according to LBC and CS methods. This study was carried out in a private pathology laboratory located in a metropolitan city, where cytological materials sent from many clinics were examined.
METHODS: There were 165,915 cases whose smears were examined between 2012 and 2020, most of them conventional (131,224 CS, 34,691 LBC). Cases were evaluated on the basis of the Bethesda 2014 classification and divided into sub-diagnostic categories after they were divided into two main groups as \"with epithelial abnormalities\" and \"without.\" χ2 and Fischer\'s precision statistical tests were conducted using SPSS 23.0 package. In the CS process, cervical samples were obtained using an endocervical brush and a spatula. Cells were directly spread onto the slides and promptly fixed in 95% ethanol, followed by staining with the standard Papanicolaou stain. For LBC ThinPrep, cervical specimens were gathered using a cervix brush. The brush was washed in a vial and discarded. Finally, cells were isolated through vacuum filtration and transferred to the slide using air pressure.
RESULTS: Squamous cell abnormalities (atypical squamous cells of undetermined significance [ASC-US], atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion [ASC-H], low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL], squamous cell carcinoma, atypical glandular cells of undetermined significance) were reported in 5,696 (3.43%) cases. ASC (ASC-US + ASC-H)/SIL ratio (1.36/2.04) was found to be 0.67 (recommended Bethesda ratio is <3). ASC-US (p < 0.001), ASC-H (p < 0.001), and HSIL(p < 0.001) detection rate of LBC was found to be significantly higher than CS. ASC-US (1.8/1.2), ASC-H (0.08/0.008), and HSIL (0.6/0.3) case ratios of LBC/CS were found to be significantly higher in LBC. LSIL (1.72/1.66) rate was similar.
CONCLUSIONS: LBC is superior to CS in detecting epithelial lesions. In addition to being used as a screening method, it is clear that it makes a great contribution to reducing cervical carcinomas due to HPV typing. Definitive comments regarding comparison of methods on reactive changes and microorganism detection are challenging. Preanalytical factors might account for these situations.

BACKGROUND: Cervical cancer is a global public health problem with high mortality. Advances in screening programs for cervical cancer are considered key to eliminate cervical cancer. We aimed to examine the contribution of cell block analysis to the detection of epithelial cell abnormalities in cervical smear samples.
METHODS: A total of 559 patients with suspected cervical pathology were examined, and their samples were analyzed by both liquid-based cytology (LBC) and cell blocks. The biopsy results of 149 out of the 559 patients were obtained.
RESULTS: Of the 50 patients who were identified as HSIL by biopsy, only 12 were diagnosed as HSIL by the LBC method, 22 as LSIL, 12 as ASCUS, and 4 as ASC-H (p < 0.001). With the cell block analysis, results for these patients were: 20 HSIL, 17 LSIL, 7 NILM, 4 \'unsatisfactory\', and 2 ASC cases (p < 0.001). LBC detected only 1 of the 10 patients with biopsy-diagnosed tumors, while 7 of these were defined as HSIL, 1 as ASCUS and 1 as AGC. The results of cell block analysis in patients with biopsy-diagnosed tumors were as follows: 7 HSIL, 1 tumor, 1 ASC and 1 LSIL.
CONCLUSIONS: Cell block analysis might be superior to LBC in terms of diagnostic accuracy in cervical pathologies, particularly in the detection of HSIL. However, both methods were similarly poor in diagnosing tumors. Cell blocks may improve diagnostic accuracy and can be a complementary method to LBC, while having the advantage of revealing histological architecture.

OBJECTIVE: This study aims to investigate the implementation rate and influencing factors of confirmatory tests for women with abnormal cervical cytology results in the Korean nationwide cervical cancer screening program.
METHODS: The National Health Insurance Service (NHIS) database was utilized to identify all Korean women who have participated in the Korean nationwide cervical cancer screening program from January 2011 and December 2021 using the NHIS database. Multiple logistic regression analysis was performed to estimate the multivariate odds ratio and evaluate the patients\' characteristics.
RESULTS: The rate of abnormal Papanicolaou (Pap) smears showed an initial increase from 2011 to 2015 and subsequently reached a plateau after 2016. When examining specific subcategories, cases of atypical squamous cells of undetermined significance (ASC-US) increased from 28,546 cases (1.1%) in 2011 to 62,850 cases (1.7%) in 2021. In contrast, cases of HSIL and SCC declined from 3,535 cases (0.14%) to 2,763 cases (0.07%) and from 383 cases (0.01%) to 179 cases (0.005%), respectively. Furthermore, the implementation rate of confirmatory tests for women with abnormal cytology increased from 8,865 cases (21.0%) in 2011 to 39,045 cases (51.2%) in 2021. Regarding the specific subcategory of ASC-US, the number of confirmatory tests exhibited a substantial increase from 4,101 cases (14.4%) in 2011 to 30,482 cases (48.5%) in 2021. For SCC, there was no significant change, with 216 cases (56.4%) in 2011 and 102 cases (57.0%) in 2021. The implementation rate of confirmatory tests was found to be significantly associated with results of abnormal Pap smear, age, and residence. Notably, economic status did not emerge as a significant factor affecting the likelihood of undergoing confirmatory tests.
CONCLUSIONS: The severity of abnormal Pap smear results is a reliable indicator of the probability of undergoing a confirmatory test. Additional endeavors are required to improve the implementation rate among women who have received abnormal Pap smear results.

OBJECTIVE: To our knowledge, there are very few studies evaluating if the levels of folate modify the risk of cervical intraepithelial neoplasia grade 2 and higher (CIN2+ and CIN3+) associated with the levels of HPV genome methylation, two cofactors related to single carbon metabolism and independently associated with cervical cancer in previous studies. We conducted a case-control study nested in a three-arm randomized clinical pragmatic trial (ASCUS-COL trial) to evaluate the risk of CIN3+ associated with methylation levels according to serum folate concentrations.
METHODS: Cases (n = 155) were women with histologically confirmed CIN2+ (113 CIN2, 38 CIN3, and 4 SCC) and controls were age and follow-up time at diagnosis-matched women with histologically confirmed ≤ CIN1 (n = 155), selected from the 1122 hrHPV + women of this trial. The concentrations of serum folate were determined by the radioimmunoassay SimulTRAC-SNB-VitaminB12/Folate-RIAKit and the methylation levels by the S5 classifier. Stepwise logistic regression models were used to estimate the association between folate or methylation levels and CIN2+ or CIN3+. The joint effect of folate levels and methylation on the risk of CIN3+ was estimated using combinations of categorical stratifications.
RESULTS: Folate levels were significantly lower in women with CIN3+ than in other diagnostic groups (p = 0.019). The risk of CIN3+ was eight times higher (OR 8.9, 95% CI 3.4-24.9) in women with folate deficiency and high methylation levels than in women with normal folate and high methylation levels (OR 1.4, 95% CI 0.4-4.6).
CONCLUSIONS: High methylation and deficient folate independently increased the risk of CIN3+ while deficient folate combined with high methylation was associated with a substantially elevated risk of CIN3+.