Role of Geminin as a Tool for Augmenting Accurate Diagnosis of Cervical Neoplasia.

AIM: To determine the role of geminin as a tool for differentiating various types of cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CC). METHODS: Seventy women newly diagnosed with CIN or CC undergoing cervical biopsy were included; their clinical profile, human papilloma virus (HPV) positivity, and colposcopy findings were noted, and biopsy tissue was analyzed for geminin content. RESULTS: On geminin immunohistochemistry, 100% of women with CIN3 and 96.29% of women with CC had geminin two plus or more. When analyzed as ordinal variables, there was a significant correlation (spearman's rho 0.35, p 0.01) between geminin and biopsy results (CIN1, CIN2, CIN3, and CC). CONCLUSIONS: Screening tests for cervical cancer, like conventional pap smears, liquid-based pap smears, and triaging with HPV, have limitations. It is important to be able to differentiate between high-grade lesions, invasive cancer, and low-grade lesions. The detection of geminin in these cells may aid in the confirmation of the diagnosis and ensure adequate treatment. Cervical intraepithelial lesions and carcinoma cervix demonstrated a correlation between increased geminin expression in CIN1 vs. CC and CIN2 vs. CC. Geminin may be a potential surrogate marker for higher-grade cervical lesions, and further research is needed to corroborate evidence in this direction.

Analysis of related factors for pathological upgrading of cervical biopsy from CIN3 to cancer after conical resection.

BACKGROUND: To investigate related factors for postoperative pathological upgrading of cervical biopsy to cervical cancer (CC) in patients with cervical intraepithelial neoplasia (CIN)3 after conical resection. METHODS: This retrospective study collected data from patients diagnosed with CIN3 by cervical biopsies at the author's Hospital between January 2012 and December 2022. The primary outcome was the pathological results of patients after conical resection. The pathological findings were categorized into the pathological upgrading group if postoperative pathology indicated CC, while those with normal, inflammatory, or cervical precancerous lesions were classified into the pathological non-upgrading group. The factors associated with upgrading were identified using multivariable logistic regression analysis. RESULTS: Among 511 patients, there were 125 patients in the pathological upgrading group (24.46%). The patients in the upgrading group were younger (47.68 ± 9.46 vs. 52.11 ± 7.02, P < 0.001), showed a lower proportion of menopausal women (38.40% vs. 53.02%, P = 0.0111), a lower proportion of HSIL (40.00% vs. 57.77%, P = 0.001), a higher rate of HPV-16/18 positive (25.60% vs. 17.36%, P = 0.011), a higher rate of contact bleeding (54.40% vs. 21.50%, P < 0.001), lower HDL levels (1.31 ± 0.29 vs. 1.37 ± 0.34 mmol/L, P = 0.002), higher neutrophil counts (median, 3.50 vs. 3.10 × 109/L, P = 0.001), higher red blood cell counts (4.01 ± 0.43 vs. 3.97 ± 0.47 × 1012/L, P = 0.002), higher platelet counts (204.84 ± 61.24 vs. 187.06 ± 73.66 × 109/L, P = 0.012), and a smaller platelet volume (median, 11.50 vs. 11.90 fL, P = 0.002).The multivariable logistic regression analysis showed that age (OR = 0.90, 95% CI: 0.86-0.94, P < 0.001), menopausal (OR = 2.68, 95% CI: 1.38-5.22, P = 0.004), contact bleeding (OR = 4.80, 95% CI: 2.91-7.91, P < 0.001), and mean platelet volume (OR = 0.83, 95% CI: 0.69-0.99, P = 0.038) were independently associated with pathological upgrading from CIN3 to CC after conical resection. CONCLUSION: Age, menopausal, contact bleeding, and mean platelet volume are risk factors of pathological upgrading from CIN3 to CC after conical resection, which could help identify high risk and susceptible patients of pathological upgrading to CC.

The association between human papillomavirus infection, vaginal microecology, and cervical intraepithelial neoplasia in women from Xinjiang, China.

PURPOSE: This study analyzes the relationship between human papillomavirus (HPV) infection, vaginal microecology, and cervical lesions to provide a basis for the prevention and treatment of cervical cancer (CC) in the Xinjiang region. METHODS: Real-time quantitative PCR was used for HPV genotyping and viral load. The Gram staining and dry biochemical enzyme kit were utilized to diagnose vaginal secretions. The χ2 test and Logistic regression analysis were used for statistical analysis. RESULTS: The HPV infection rate among women in the Xinjiang region was 30.29%, of which the single HPV infection accounts for 77%. HPV16 and HPV52 were the main infection types. There was significant differences in the HPV infection rate and infection types among the Han, Uighur, Hui, and Kazakh ethnic groups. The viral load of HPV16 and HPV52 increases with the upgrade of cervical lesions. There were significant differences in vaginal microecology evaluation indicators H2O2, SNA, LE, GUS, trichomonas, clue cells, and lactobacilli among different ethnic groups. HPV negative patients with varying grades of cervical lesions exhibit a notable variance in H2O2 and LE, which is statistically significant. Single HPV infection and high viral load HPV significantly increase the risk of CC. CONCLUSIONS: This study indicates that HPV infection and vaginal microecology differ among ethnic groups, which have a strong correlation with the progression of CC, offering guidance on CC screening and interventions in the Xinjiang area.

Clinical characteristics, HPV involvement, and demographic risk factors in women with cervical intraepithelial neoplasia complicated by vaginal intraepithelial neoplasia.

PURPOSE: This study aimed to explore the clinical characteristics and risk factors associated with cervical intraepithelial neoplasia (CIN) when coexisting with vaginal intraepithelial neoplasia (VAIN). METHODS: We analyzed the clinical data of 212 patients diagnosed with CIN, including 50 patients with concurrent VAIN. The groups were compared to identify distinct clinical features and independent risk factors for the co-occurrence of CIN and VAIN, using logistic regression analysis. RESULTS: Patients with both CIN and VAIN had a median age of 57, significantly older than the 41-year median age of patients with CIN only (P < 0.05). A higher prevalence of HPV infection (98.0%) was observed in the CIN and VAIN group, with a notable rate of multiple HPV infections (67.3%) compared to the CIN-only group (P < 0.05). Educational levels were significantly lower in the combined CIN and VAIN group (P < 0.05). HPV16, 33, and 52 were identified as significant types for single and multiple infections. Multivariate analysis confirmed age as an independent risk factor for CIN with VAIN (P < 0.05). VAIN3 patients were more likely to exhibit HSIL and ASC-H, whereas VAIN1 cases tended to correspond with ASCUS and LSIL diagnoses. CONCLUSION: The co-occurrence of CIN and VAIN is significantly influenced by patient age and educational level. The findings advocate for more diligent vaginal examination during colposcopy in older patients, particularly those with multiple HPV infections and cytological abnormalities, to enhance the early detection of vaginal lesions and prevent missed diagnoses and treatments. Additionally, the high prevalence of HPV infection, especially with certain types, underscores the importance of HPV monitoring in this patient population.

Reevaluation of negative cervical conizations: Frequency, diagnostic errors, risk factors and management.

OBJECTIVE: Cervical conization is an effective treatment for precancerous lesions. However, in cases where no high-grade lesion is identified in the surgical specimen, managing these patients may be challenging due to the absence of established follow-up protocols for negative conizations. This study aimed to assess the negative conization rates at our institution by histopathological review, identify diagnostic errors, possible risk and recurrence factors and propose follow-up strategies for this group of patients. METHODS: A retrospective study from January-2010 to December-2020 analyzed patients with negative conization including all surgical techniques and procedure indications. Biopsy and cervical conizations slides were reviewed and patients who kept a negative result underwent deeper levels sectioning of the paraffin blocks with immunohistochemical stains application: p16, Ki-67 and geminin. Data were compared with a control group composed by 29 women with CIN3. RESULTS: Out of 1022 conizations, 186 were negative (18.1%), with 151 cases selected for the study after excluding 35 patients. Following pathology review, 4 patients were excluded due to false-positive cervical biopsy results, 16 for false-negative conization results and 9 for hidden dysplasia identified after deeper sectioning. The remaining 122 patients were considered truly negative cones (11.9%) and exhibited IHC staining with p16 positive in 20.4% of cases, low Ki-67 expression, and low geminin score in most cases. Specimens with CIN 1 had higher prevalence of p16 staining, Ki-67 expression and geminin score when compared to absence of neoplasia, nevertheless geminin had no statistical difference. Older age, higher parity and IHC pattern with negative p16, low Ki-67 and geminin expressions were identified as risk factors for negative cones (p<0.05). Only 10 patients recurred for high-grade lesions, with no statistically significant risk factors identified. CONCLUSIONS: The negative conization rate was 11.9%, with diagnostic errors identified across pre-surgical biopsy, cone specimen, and deeper levels. Risk factors included older age, higher parity, low expression of p16, Ki-67 and geminin (p<0.05). Recurrence represented 8.1% of the negative cones, without identification of statistically significant risk factors. Pathological review with deeper level sections and 2-year follow-up are recommended for patients with negative conizations.

Characterization of genital chlamydia trachomatis infection among women attending infertility and gynecology clinics in Hunan, China.

BACKGROUND: Genital infection with Chlamydia trachomatis (C. trachomatis) is a major public health issue worldwide. It can lead to cervicitis, urethritis, and infertility. This study was conducted to determine the characteristics of genital C. trachomatis infection among women attending to the infertility and gynecology clinics. METHODS: Endocervical swabs were collected from 8,221 women for C. trachomatis nucleotide screening and genotyping, while serum samples were collected for C. trachomatis pgp3 antibody determination using luciferase immunosorbent assays. RESULTS: High C. trachomatis DNA prevalence (3.76%) and seroprevalence (47.46%) rates were found, with genotype E (27.5%) being the most prevalent. C. trachomatis omp1 sense mutation was associated with cervical intraepithelial neoplasia (CIN) (odds ratio [OR] = 6.033, 95% confidence interval [CI] = 1.219-39.185, p = 0.045). No significant differences in C. trachomatis seroprevalence rates were observed between women with detectable C. trachomatis DNA in the infertility and routine physical examination groups (86.67% vs. 95%, p > 0.05); however, among women with negative C. trachomatis DNA, the former group had a markedly higher seroprevalence than the latter group (56.74% vs. 20.17%, p < 0.001). C. trachomatis DNA, but not pgp3 antibody, was significantly associated with CIN (OR = 4.087, 95% CI = 2.284-7.315, p < 0.001). CONCLUSION: Our results revealed a high prevalence, particularly seroprevalence, of C. trachomatis among women with infertility. Furthermore, we found an association between C. trachomatis omp1 sense mutations and CIN. Therefore, C. trachomatis serves as a risk factor for CIN.

MFEM-CIN: A Lightweight Architecture Combining CNN and Transformer for the Classification of Pre-Cancerous Lesions of the Cervix.

Goal: Cervical cancer is one of the most common cancers in women worldwide, ranking among the top four. Unfortunately, it is also the fourth leading cause of cancer-related deaths among women, particularly in developing countries where incidence and mortality rates are higher compared to developed nations. Colposcopy can aid in the early detection of cervical lesions, but its effectiveness is limited in areas with limited medical resources and a lack of specialized physicians. Consequently, many cases are diagnosed at later stages, putting patients at significant risk. Methods: This paper proposes an automated colposcopic image analysis framework to address these challenges. The framework aims to reduce the labor costs associated with cervical precancer screening in undeserved regions and assist doctors in diagnosing patients. The core of the framework is the MFEM-CIN hybrid model, which combines Convolutional Neural Networks (CNN) and Transformer to aggregate the correlation between local and global features. This combined analysis of local and global information is scientifically useful in clinical diagnosis. In the model, MSFE and MSFF are utilized to extract and fuse multi-scale semantics. This preserves important shallow feature information and allows it to interact with the deep feature, enriching the semantics to some extent. Conclusions: The experimental results demonstrate an accuracy rate of 89.2% in identifying cervical intraepithelial neoplasia while maintaining a lightweight model. This performance exceeds the average accuracy achieved by professional physicians, indicating promising potential for practical application. Utilizing automated colposcopic image analysis and the MFEM-CIN model, this research offers a practical solution to reduce the burden on healthcare providers and improve the efficiency and accuracy of cervical cancer diagnosis in resource-constrained areas.

Aerobic vaginitis is associated with carbonic anhydrase IX in cervical intraepithelial neoplasia.

The aim of this study was to analyze the association between vaginal microbiota, carbonic anhydrase IX (CAIX) and histological findings of cervical intraepithelial neoplasia (CIN). The study included 132 females, among them 66 were diagnosed with high-grade intraepithelial lesion (CIN2, CIN3, and cancer), 14 with low-grade disease, and 52 assigned to the control group. An interview focused on the behavior risk factors, together with vaginal fluid pH measurement, wet mount microscopy, detection of Chlamydia trachomatis, and Trichomonas vaginalis were performed. After colposcopy, high-grade abnormalities were detected via direct biopsies and treated with conization procedure. Conuses were immuno-stained with CAIX antibody. The histological findings were CIN1 (n = 14), and CIN2+ (included CIN2 (n = 10), CIN3 (n = 49), and cancer (n = 7; squamous cell carcinomas)). Prevalence of bacterial vaginosis (BV) was similar between the groups. Moderate or severe aerobic vaginitis (msAV) was diagnosed more often among CIN2+ (53.0%) than CIN1 (21.4%). Moderate or strong immunostaining of CAIX (msCAIX) was not detected among CIN1 cases. Thus, msAV was prevalent in CAIX non-stained group (p = 0.049) among CIN2 patients. Co-location of msAV and msCAIX was found in CIN3. Regression model revealed that msAV associated with high-grade cervical intraepithelial neoplasia independently from smoking and the number of partners.

Diagnostic value of HPV E6/E7 mRNA in screening for cervical intraepithelial neoplasia grade 2 or worse: A systematic review and meta­analysis.

Histology is considered the gold standard for diagnosing the pathological progress of cervical cancer development, while cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) is the cutoff for intervention in clinical practice. The diagnostic value of human papillomavirus (HPV) E6/E7 mRNA in screening for CIN2+ has not been systematically summarized. A meta-analysis was conducted as part of the present study conducted to explore the diagnostic value of HPV E6/E7 mRNA in screening for CIN2+, aiming to provide a new marker for earlier clinical diagnosis of cervical cancer. The PubMed, Embase and Cochrane Library databases were searched from inception to May 2023. Studies reporting the true positive, false positive, true negative and false negative values in differentiating between CIN2+ and CIN2- were included, while duplicate publications, studies without full text, incomplete information or inability to conduct data extraction, animal experiments, reviews and systematic reviews were excluded. STATA software was used to analyze the data. A total of 2,224 patients were included of whom there were 1,274 patients with CIN2+ and 950 patients with CIN2-. The pooled sensitivity and specificity of the studies overall were 0.89 (95% CI, 0.84-0.92) and 0.59 (95% CI, 0.46-0.71), respectively; the positive likelihood ratio (LR) and the negative LR of the studies overall were 2.31 (95% CI, 1.61-3.32) and 0.21 (95% CI, 0.14-0.30), respectively. The pooled diagnostic odds ratio of the studies overall was 11.53 (95% CI, 6.85-19.36). Additionally, the area under the curve was 0.88. The analysis indicated that HPV E6/E7 mRNA has high diagnostic efficacy for CIN2+. HPV E6/E7 mRNA is highly sensitive in the diagnosis of CIN2+, which helps to reduce the rate of missed diagnoses. However, lower specificity may lead to a higher number of misdiagnoses in healthy patients.

Association between serum P16ink4A concentration and CIN and cervical cancer among women attending a cervical cancer clinic in western Uganda: A case control study.

Introduction: Tissue expression of P16ink4A is correlated with cervical lesions. In this study we determined the association between serum P16ink4A concentrations and cervical lesions among women attending the cervical cancer clinic at Mbarara Regional Hospital (MRRH) South Western Uganda. Material and Methods: We recruited 90 cervical intraepithelial neoplasia (CIN) cases, 90 cervical cancer (CC) cases before treatment and 90 controls. Clinical and demographic data were recorded. Serum P16ink4A concentrations were measured by quantitative Elisa. Cases were confirmed with cytology and/or histology. Descriptive statistics and logistic regression were done with STATA 17 and P-values of <0.05 were considered statistically significant. Results: The mean serum P16ink4A concentration among CIN cases, CC cases and controls was 1.11(+/-0.66) ng/ml, 1.45(+/-1.11) ng/ml and 1.13(+/-0.61) ng/ml respectively (p = 0.008). 50 % of CIN cases and controls as well as 60 % of CC cases had P16ink4A concentration above 0.946 ng/ml. There were increased odds of CIN for serum P16ink4A though statistically insignificant (AOR: 1.11, p-value: 0.70). There was also a statistically significant reduction in odds of CC for serum P16ink4A (AOR: 0.55, p-value: 0.01). Conclusion: Serum P16ink4A may likely be associated with cervical lesions especially CC in our study population and this may aid detection of such lesions. Diagnostic utility studies for circulating P16ink4A in detection of cervical cancer are recommended.

Impact of artificial intelligence on the diagnosis, treatment and prognosis of endometrial cancer.

Endometrial cancer is one of the most prevalent tumours in females and holds an 83% survival rate within 5 years of diagnosis. Hypoestrogenism is a major risk factor for the development of endometrial carcinoma (EC) therefore two major types are derived, type 1 being oestrogen-dependent and type 2 being oestrogen independent. Surgery, chemotherapeutic drugs, and radiation therapy are only a few of the treatment options for EC. Treatment of gynaecologic malignancies greatly depends on diagnosis or prognostic prediction. Diagnostic imaging data and clinical course prediction are the two core pillars of artificial intelligence (AI) applications. One of the most popular imaging techniques for spotting preoperative endometrial cancer is MRI, although this technique can only produce qualitative data. When used to classify patients, AI improves the effectiveness of visual feature extraction. In general, AI has the potential to enhance the precision and effectiveness of endometrial cancer diagnosis and therapy. This review aims to highlight the current status of applications of AI in endometrial cancer and provide a comprehensive understanding of how recent advancements in AI have assisted clinicians in making better diagnosis and improving prognosis of endometrial cancer. Still, additional study is required to comprehend its strengths and limits fully.

Knowledge of cytology results affects the performance of colposcopy: a crossover study.

OBJECTIVE: To determine whether knowledge of cytology affects the colposcopist's diagnostic accuracy in the identification of cervical intraepithelial neoplasia grade 2 and worse (≥ CIN2). METHOD: In this cross-over study, healthcare professionals interpreted colposcopy images from 80 patient cases with known histological diagnoses. For each case, 2 images taken with a colposcope were provided (native and after acetic acid application). Inclusion criteria consisted of women with a transformation zone type 1 or 2, who had both a cytological and histological diagnosis. Cases were distributed across two online surveys, one including and one omitting the cytology. A wash-out period of six weeks between surveys was implemented. Colposcopists were asked to give their diagnosis for each case as < CIN2 or ≥ CIN2 on both assessments. Statistical analysis was conducted to compare the two interpretations. RESULTS: Knowledge of cytology significantly improved the sensitivity when interpreting colposcopic images, from 51.1% [95%CI: 39.3 to 62.8] to 63.7% [95%CI: 52.1 to 73.9] and improved the specificity from 63.5% [95%CI: 52.3 to 73.5] to 76.6% [95%CI: 67.2 to 84.0]. Sensitivity was higher by 38.6% when a high-grade cytology (ASC-H, HSIL, AGC) was communicated compared to a low-grade cytology (inflammation, ASC-US, LSIL). Specificity was higher by 31% when a low-grade cytology was communicated compared to a high-grade. CONCLUSIONS: Our data suggests that knowledge of cytology increases sensitivity and specificity for diagnosis of ≥ CIN2 lesions at colposcopy. Association between cytology and histology may have contributed to the findings.

YAP/TAZ-TEAD activity promotes the malignant transformation of cervical intraepithelial neoplasia through enhancing the characteristics and Warburg effect of cancer stem cells.

A number of studies have confirmed that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)-transcriptional enhanced associate domain (TEAD) activity is the driver of cancer development. However, the role and mechanism of the YAP/TAZ-TEAD pathway in cervical intraepithelial neoplasia (CIN) remain to be clarified. Therefore, this study was designed to observe the effect of YAP/TAZ-TEAD activity on the development of CIN and provide new ideas for the diagnosis and treatment of CIN. Firstly, cervical tissues were collected from CIN patients in different stages [CIN grade 1 (CIN1) tissue, CIN grade 2/3 (CIN 2/3) and squamous cell carcinoma (SCC)] and healthy volunteers. Next, the expression levels of YAP, TAZ and TEAD in cervical tissues and cells were observed by immunohistochemistry, qRT-PCR and western blot. Besides, Z172 and Z183 cells were transfected with siRNA-YAP/TAZ (si-YAP/TAZ) and YAP/TAZ overexpression vector (YAP-5SA). Also, Z172 cells were co-transfected with YAP-5SA and si-TEAD2/4. Subsequently, the stemness characteristics, glycolysis level and malignant transformation of cells in each group were observed by sphere-formation assay, commercial kit, MTT, Transwell, scratch experiment, xenotransplantation and western blot.The expression of YAP, TAZ and TEAD increased significantly in cervical cancer tissue and cell line at the stage of CIN2/3 and SCC. When YAP/TAZ was knocked down, the stemness characteristics, glycolysis level and malignant transformation of cancer cells were notably inhibited; while activating YAP/TAZ exhibited a completely opposite result. In addition, activating YAP/TAZ and knocking down the TEAD expression at the same time significant weakened the effect of activated YAP/TAZ signal on precancerous cells and reduced inhibitory effect of knocking down TEAD alone. YAP/TAZ-TEAD signal activates the characteristics and Warburg effect of cancer stem cells, thereby promoting the malignant transformation of CIN.

Topical imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia lesions (TOPIC-2): A randomised controlled trial.

OBJECTIVE: To investigate the efficacy of imiquimod in women with residual or recurrent cervical intraepithelial neoplasia (rrCIN), compared with large loop excision of the transformation zone (LLETZ). DESIGN: Randomised controlled non-inferiority trial. SETTING: One academic and one regional hospital in the Netherlands. POPULATION: Thirty-five women with rrCIN were included in the study between May 2016 and May 2021. METHODS: Women were randomised to receive treatment with 5% imiquimod cream (12.5 mg) intravaginally (three times a week for a duration of 16 weeks) or a LLETZ procedure (standard treatment). MAIN OUTCOME MEASURES: The primary outcome was reduction to normal cytology at 6 months after starting treatment. Secondary outcomes were clearance of high-risk human papilloma virus (hr-HPV) in both groups and reduction to ≤CIN1 in the imiquimod group. Side effects were monitored. RESULTS: Treatment success was 33% (6/18) in the imiquimod group versus 100% (16/16) in the LLETZ group (P < 0.001), whereas HPV clearance was 22% (4/18) in the imiquimod group versus 88% (14/16) in the LLETZ group (P < 0.001). After the randomisation of 35 women, the futility of treatment with imiquimod was proven and the trial was prematurely finished. In the follow-up period, three patients remained without additional treatment, whereas all other patients underwent LLETZ, conisation or hysterectomy. In the LLETZ group none of the patients received additional treatment during 2 years of follow-up. CONCLUSIONS: This is the first randomised controlled trial to show that topical imiquimod has a significantly lower success rate in terms of reduction to normal cytology and hr-HPV clearance, compared with LLETZ, in women with rrCIN. Additionally, imiquimod has numerous side effects and after using imiquimod most women with rrCIN still required additional surgical treatment.

Comparison of Colposcopy and Histopathology in Abnormal Cervix.

Cervicovaginal cancer (CVC) is the most common malignancy of the genital tract. Colposcopy is a diagnostic procedure that is used to examine the cervix and tissue samples of the urethra and vulva in a magnified view. The colposcopy and histological findings of unhealthy cervixes in a tertiary care hospital were compared. This comparative cross-sectional study was conducted from November 2022 to March 2023 among women with a variety of gynecological complaints who visited the Department of Obstetricians and Gynecologists in a tertiary care facility. One hundred participants were included in this study. The data collected were analyzed using Microsoft Excel 2016 (Microsoft Corporation, Redmond, Washington, United States). Participants had an average age of 35.22 ± 7.18 years, and white discharge was the most reported ailment (73%). Comparing the results of the colposcopy with the histological findings revealed a sensitivity of 91.5% and a specificity of 72.2%. The high sensitivity of colposcopy highlights the need to combine it with histological techniques to obtain better results.

Human Papilloma Virus Typing as a Triage Tool for Women with Postcoital Bleeding: A Retrospective Cohort Study.

Objective: To investigate the performance of human papilloma virus (HPV) typing as a triage tool in the management of patients with postcoital bleeding (PCB). Methods: All patients referred for colposcopy at a cervical pathology clinic of a nationwide health insurance organization, due to PCB and had a preceding high-risk HPV (hrHPV) test between 2018 and 2020, were retrospectively located. Demographic and pathologic data were collected from electronic medical files. Sensitivity, specificity, and negative and positive predictive value of hrHPV test according to final pathology were calculated. Results: Three hundred ninety patients referred for colposcopy due to PCB with a preceding hrHPV test were located. HrHPV-positive patients were significantly younger (33.7 ± 10 vs. 37.2 ± 9, p < 0.006) with a higher proportion of nulliparous, nonmarried, and smokers compared with hrHPV-negative patients (75% vs. 47%, p < 0.001; 75.4% vs. 45.1%, p < 0.001; and 24.6% vs. 12.8%, p < 0.028, respectively). No case of high-grade cervical intraepithelial neoplasia (CIN2/3) was identified among hrHPV-negative patients. The sensitivity and NPV of the hrHPV test for high-grade cervical lesions were both 100%, decreasing to 36% and 95%, respectively, for any cervical dysplasia (CIN1/CIN2/CIN3). Adding cytology to HPV typing had a negligible effect on test performance. At univariate analysis, age, HPV vaccine status, nulliparity, and positive HPV typing were independently associated with cervical dysplasia. At multivariate analysis, only positive HPV typing remained significantly associated with cervical dysplasia (hazard ratio 2.75, confidence interval 1.1-6.5, p = 0.023). Conclusion: A negative HPV test even in the presence of PCB may rule out cervical dysplasia with extremely high accuracy and may save unnecessary colposcopies.

Correlation between P16/Ki67 in cervical cytology and diagnosis of cervical intraepithelial neoplasia 2-3 in Thai women infected with high-risk types of human papillomavirus.

OBJECTIVES: The addition of p16/Ki-67 dual immunostaining to human papilloma virus (HPV) screening tests has been shown to increase the detection rate of high-grade cervical intraepithelial neoplasia. Thus, the aim of this study was to evaluate the accuracy of p16/Ki67 dual staining in the detection of cervical intraepithelial neoplasia 2 (CIN2+) in women with high-risk HPV infection. MATERIALS AND METHODS: A cross-sectional study was conducted between August 2017 and August 2019 at the Chulabhorn Hospital in Bangkok, Thailand. Women aged 20-70 years who underwent co-testing and tested positive for high-risk (HR) HPV (N = 215) were invited to participate in the study. P16/Ki67 testing was performed on residual cytological materials. Colposcopic biopsies were performed on all patients, and the results were correlated with positive or negative p16/Ki-67 test results. RESULTS: The sensitivity and specificity of p16/Ki-67 dual staining in the detection of CIN2+ in the women with HR HPV infection were 74.4 % and 63.4 %, respectively. Compared with liquid-based cytology (LBC), p16/Ki67 cytology had similar sensitivity (p = 1.000) and specificity (p = 0.561) to LBC for detecting CIN2+. CONCLUSION: In this study, p16/Ki67 dual staining in HPV triage demonstrated a test performance similar to that of LBC.

Successful pregnancy and delivery after HiPorfin photodynamic therapy for cervical high-grade squamous intraepithelial lesion.

OBJECTIVE: The study analyzed HiPorfin-Photodynamic therapy (PDT) for young women with cervial high-grade squamous intraepithelial lesion (HSIL) and evaluated the impact of PDT on their pregnancy and delivery. METHODS: Retrospective analysis of 4 patients (21-33 years old) were treated with HiPorfin® (2 mg/kg) PDT in 2019-2022. 1 patient suffered from cervical intraepithelial neoplasia (CIN)Ⅱ and 3 patients from CIN Ⅲ. 630 nm laser light irradiated the cervical surface and endocervical canal with light dose of 150 J/cm2 and 100-120 J/cm2 respectively. RESULTS: The median observation time period was 40.5 months. Cure rate, HPV eradication rate and negative conversion rate of cytology were all 100.0 % at 3, 6 and 12 months. All cervical canal lesions completely turned negative. No recurrence occurred during the long-term follow-up period. None of patients suffered from infertility. Three patients delivered vaginally and one delivered by C-section to healthy infants at term. CONCLUSION: HiPorfin® PDT for cervical HSIL was proved to be a safe method without adverse effects on female fertility and allowing these women to have healthy, full-term children.

Cervicovaginal microbiota long-term dynamics and prediction of different outcomes in persistent human papillomavirus infection.

Persistent human papillomavirus (HPV) infection can lead to cervical intraepithelial neoplasia (CIN) and cervical cancer, posing serious threats to the health of women. Although the cervicovaginal microbiota is strongly associated with CIN, the dynamics of the microbiota during CIN development are unknown. In this retrospective cohort study, we analyzed 3-year longitudinal data from 72 patients diagnosed with a persistent HPV infection almost all caused by high-risk HPV types. Patients were categorized into groups with HPV persistent infection (n = 37), progression to CIN (n = 16), and CIN regression (n = 19) based on infection outcome during the follow-up period. Furthermore, 16S rRNA gene sequencing was performed on consecutively collected cervical samples to explore the composition and dynamics of the cervicovaginal microbiota during the development and regression of CIN. Our results showed that the composition of the cervicovaginal microbiota varied among women with different HPV infection outcomes and remained relatively stable during the follow-up period. Notably, the serial follow-up data showed that these microbial alterations were present for at least 1-2 years and occurred before pathologic changes. In addition, microbial markers that were highly discriminatory for CIN progression or regression were identified. This study provides evidence for a temporal relationship between changes in the cervicovaginal microbiota and the development of CIN, and our findings provide support for future microbial intervention strategies for CIN.

A retrospective study for long-term oncologic and obstetric outcomes in cervical intraepithelial neoplasia treated with loop electrosurgical excision procedure: focus on surgical margin and human papillomavirus.

BACKGROUND: The present study aimed to evaluate the long-term oncological and obstetric outcomes following the loop electrosurgical excision procedure (LEEP) in patients with cervical intraepithelial neoplasia (CIN) and investigate the risk factors for recurrence and preterm birth. METHODS: This retrospective cohort study included patients who underwent LEEP for CIN 2-3 between 2011 and 2019. Demographic information, histopathological findings, postoperative cytology, and human papillomavirus (HPV) status were collected and analyzed. The Cox proportional hazards model and Kaplan-Meier curves with the log-rank test were used for risk factor analysis. RESULTS: A total of 385 patients treated with the LEEP were analyzed. Treatment failure, including recurrence or residual disease following surgery, was observed in 13.5% of the patients. Positive surgical margins and postoperative HPV detection were independent risk factors for CIN1 + recurrence or residual disease (HR 1.948 [95%CI 1.020-3.720], p = 0.043, and HR 6.848 [95%CI 3.652-12.840], p-value < 0.001, respectively). Thirty-one patients subsequently delivered after LEEP, and the duration between LEEP and delivery was significantly associated with preterm-related complications, such as a short cervix, preterm labor, and preterm premature rupture of the membrane (p = 0.009). However, only a history of preterm birth was associated with preterm delivery. CONCLUSIONS: Positive HPV status after LEEP and margin status were identified as independent risk factors for treatment failure in patients with CIN who underwent LEEP. However, combining these two factors did not improve the prediction accuracy for recurrence.