Search

Objective: Laser vaporization is less invasive than conization for cervical intraepithelial neoplasia (CIN). The outcome of laser vaporization for CIN is empirically known to depend on the colposcopic findings, especially localization of the lesion. In this study, we sought to identify factors involved in the outcome of laser vaporization., Materials and Methods: We retrospectively investigated 290 cases of CIN (CIN2, n = 180; CIN3, n = 110) treated with laser evaporation at Nishikawa Women's Health Clinic between 2018 and 2021. All treatments were performed using a carbon dioxide laser under either colposcopic vision (n = 172) or direct vision using a vaginal speculum (n = 118). Risk factors were statistically examined for cure rate after treatment., Results: Multivariate analysis using a logistic regression model identified independent factors affecting the success of treatment to be high-risk human papillomavirus infection status preoperatively, CIN grade, presence of CIN lesions at the periphery of the cervix, and the surgical method used. Colposcopy-guided laser vaporization reduced the risk of treatment failure by 84% (odds ratio 0.16, 95% confidence interval 0.06-0.46; p = 0.001) compared with direct vision using a vaginal speculum. For lesions at the periphery of the cervix, most of the treatment failures were in the group that was not guided by colposcopy (p = 0.031)., Conclusion: The presence of a peripheral CIN lesion was suggested to be a risk factor for treatment failure. Laser vaporization under colposcopic vision is recommended for treatment of peripheral CIN lesions., Competing Interests: Conflicts of interest All authors report no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background/aim: Pleomorphic high-grade squamous intraepithelial lesions (PHSILs) of the uterine cervix are characterized by strikingly pleomorphic and enlarged nuclei with brisk mitotic activity. The aim of this study was to analyze the clinical outcomes of patients with PHSIL., Patients and Methods: Clinical data were collected from the electronic medical records of 44 patients with PHSIL., Results: The patients' mean age was 52.1 years. The initial cytological diagnosis was HSIL in 43.2% of patients. High-risk human papillomavirus was detected in 89.5% of patients. The human papillomavirus type was not predominated by one specific type. The patients were treated with conization alone or with conization with subsequent hysterectomy. Two cases of squamous cell carcinoma coexisting with PHSIL, and one case of adenoid basal carcinoma were detected among the surgical specimens. Follow-up cytology revealed negative results for intraepithelial lesions in all patients, except for one patient who experienced recurrent PHSIL 41 months after hysterectomy and underwent laser ablation., Conclusion: The incidence rates of concurrent squamous cell carcinoma (4.5%) and recurrence (2.3%) in our PHSIL cohort were lower than those previously reported in patients with conventional HSIL. Our findings suggest that pleomorphic nuclear change alone in PHSIL was not associated with worse clinical outcomes than conventional HSIL and support the notion that PHSIL does not require more aggressive clinical management than conventional HSIL. However, close follow-up with cytological examination may be necessary to determine the potential risk of recurrence., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Although therapeutic human papillomavirus vaccines could offer a noninvasive treatment for patients with cervical intraepithelial neoplasia, none has been clinically implemented. Oral administration of the therapeutic human papillomavirus vaccine IGMKK16E7 results in the histological regression of human papillomavirus 16-positive cervical intraepithelial neoplasia 2/3 to normal (complete response). We investigated biomarkers that could predict complete response after oral administration of IGMKK16E7., Methods: Forty-two patients administered high-dose oral IGMKK16E7 in a phase I/II trial were included. Cervix-exfoliated cells were collected before vaccine administration. Gene expression of CD4, CD8, FOXP3, programmed cell death 1 protein, CTLA4, CD103, CD28, CD80, CD86, and programmed cell death 1 ligand 1 in the cells was measured by quantitative reverse transcriptase-polymerase chain reaction. Receiver operating characteristic curve analysis and Mann-Whitney tests were used to explore potential biomarkers. Pearson correlation coefficient analysis was used to correlate gene expression profiles with clinical outcome., Results: The only predictive biomarker of vaccine response for which receiver operating characteristic curve analysis showed significant diagnostic performance with histological complete response was CD86 (area under the curve = 0.71, 95% confidence interval = 0.53 to 0.88, P = .020). Patients with complete response had significantly lower CD86 expression (CD86-low) than patients with no complete response (P = .035). The complete response rates for CD86-low and CD86-high patients were 50% and 19%, respectively, and CD86-low patients had a significantly higher complete response rate (P = .047). Compared with all patients, the CD86-low group had a 1.5-fold increase in the complete response rate. Gene expression of CD86 and CTLA4 showed the strongest positive correlation with clinical outcomes in the incomplete response group (P < .001)., Conclusion: Low expression of CD86 in exfoliated cervical cells can be used as a pretreatment biomarker to predict histological complete response after IGMKK16E7 administration., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Adenocarcinoma in situ (AIS) of the cervix can progress to invasive adenocarcinoma. While hysterectomy is standard, conservative management may be considered for women desiring future pregnancies. This study aimed to determine the prevalence of residual disease in hysterectomy specimens following excisional therapy with clear margins for AIS., Methods: A retrospective FRANCOGYN cohort study was conducted on patients who underwent a hysterectomy after conization with clear margins for AIS between 2008 and 2021. The primary goal was to assess the prevalence of residual disease in the hysterectomy specimens. Secondary objectives included identifying preoperative predictors of residual disease and comparing recurrence rates between patients with and without residual disease., Results: Of 53 hysterectomies performed after conization with negative margins for AIS, 20.8% (11/53) showed residual disease in the final histology. None of the patients had invasive cancer. In the residual disease group, 18% (2/11) had persistent CIN 3, and 82% (9/11) had persistent AIS. These patients tended to have higher BMI (27.5 kg/m² vs. 23.6 kg/m², p=0.04) and shorter endocervical margins (2mm vs. 5mm, p=0.01). No recurrences were observed during follow-up., Conclusion: Despite clear margins on the initial conization for AIS, 20% of patients had residual disease in their hysterectomy samples, though no invasive cancer was found. A hysterectomy should be considered after completing childbearing, even if initial margins are clear., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: We aimed to investigate differences between HPV-16 mono- and HPV-16/18 co-infections in terms of cervical dysplasia and invasive cancer., Methods: This multicentre, retrospective study spanned from December 2017 to December 2020, involving women who visited gynaecological oncology clinics for colposcopy with either HPV-16 or HPV-16/18 positivity. A total of 736 patients, 670 in Group 1 (HPV-16 positivity) and 66 in Group 2 (HPV-16/18 positivity), were compared for the presence of CIN2+ lesions detected by colposcopic biopsy or endocervical curettage (ECC). Exclusions included hysterectomized patients, those with prior gynaecological cancers, and patients with HPV positivity other than types 16 and 18., Results: Among the included patients, 42.4% had a diagnosis of CIN2+ lesions. The cytology results demonstrated abnormal findings in 45.3% in Group 1 and 42.2% in Group 2, with no significant difference between the groups. ECC revealed CIN2+ lesion in 49 (8.7%) patients in group 1, while only 1 (1.7%) patient had CIN2+ lesion in group 2. There was no difference between 2 groups in terms of ECC result (p = 0.052). In group 1, 289 (43.1%) patients had CIN2+ lesion, while 23 (34.8%) patients had CIN2+ lesions in group 2. There was no difference between group 1 and 2 in terms of diagnosis of CIN2+ lesions (p = 0.19)., Conclusion: This multicentre retrospective study found no significant differences between HPV-16 mono- and HPV-16/18 co-infections regarding cervical pathologies. Larger studies are needed to validate and further explore these findings., (© 2024 John Wiley & Sons Ltd.)

Background: AICyte has previously demonstrated a potential role in cervical cytology screening for reducing the workload by using a 50% negative cutoff value. The aim of the current study is to evaluate this hypothesis., Methods: The authors used the Ruiqian WSI-2400 (with the registered trademark AICyte) to evaluate a collection of 163,848 original cervical cytology cases from 2018 to 2023 that were collected from four different hospital systems in China. A breakdown of cases included 46,060 from Shenzhen, 67,472 from Zhengzhou, 25,667 from Shijiazhuang, and 24,649 from Jinan. These collected cases were evaluated using the AICyte system, and the data collected were statistically compared with the original interpretative results., Results: In 98.80% of all artificial intelligence cases that were designated as not needing further review, the corresponding original diagnosis was also determined to be negative. For any cases that were designated atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion or higher, the sensitivity and negative predictive value were 90.77% and 98.80%, respectively. The sensitivity and negative predictive value were greater in cases designated as low-grade squamous intraepithelial lesion or higher at 98.92% and 99.94%, respectively. Of the 49 low-grade squamous intraepithelial lesion or higher that were designed by AICyte as not needing further review, the cytohistologic correlation revealed eight cases of cervical intraepithelial neoplasia 1 and 18 negative cases; and the remaining cases were without histologic follow-up. In practice, AICyte used at a 50% negative cutoff value could reduce the anticipated workload if a protocol were implemented to label cases that qualified within the negative cutoff value as not needing further review, thereby finalizing the case as negative for intraepithelial lesions and malignancy., Conclusions: For pathologic practices that do not have cytotechnologists or in which the workflow is sought to be optimized, the artificial intelligence system AICyte alone to be an independent screening tool by using a 50% negative cutoff value, which is a potential assistive method for cervical cancer screening., (© 2024 The Author(s). Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: Over the past decade, liquid-based cytology has replaced conventional cytology for cervical cancer screening in many countries, including Japan. We aimed to evaluate the efficacy of liquid-based cytology using a large database and compare two major liquid-based cytology platforms, SurePath and ThinPrep, to conventional cytology., Methods: Cervical cancer screening data were collected from the Japan Cancer Society between 2015 and 2019. The efficacy of liquid-based and conventional cytology in detecting cervical intraepithelial neoplasia (CIN) was evaluated. Detection rates and positive predictive values were compared using a Poisson regression model., Results: We collected data of 3,918,149 participants, including 2,248,202 conventional cytology, 874,807 SurePath and 795,140 ThinPrep smears. The detection rate of CIN2 or more was 1.14 times higher using SurePath than that using conventional cytology (95% confidence interval [CI], 1.09-1.20; p < 0.001). Contrastingly, the detection rate of CIN2 or more was 0.91 times lower using ThinPrep (95% CI, 0.86-0.96; p < 0.001). The detection rates of CIN3 or more did not differ significantly between SurePath and conventional cytology (detection rate ratio, 1.04; 95% CI, 0.97-1.12; p = 0.224). The positive predictive value ratios of CIN2 or more were 0.80 using SurePath (95% CI, 0.76-0.84; p < 0.001) and 0.83 using ThinPrep (95% CI, 0.79-0.87; p < 0.001) compared with conventional cytology., Conclusions: Liquid-based cytology, particularly SurePath, was useful for detecting CIN2 or higher in population-based cervical cancer screening. Further widespread use of liquid-based cytology methods would lead to efficient detection of cervical precancerous lesions., (© 2024 The Author(s). Cytopathology published by John Wiley & Sons Ltd.)

Cervical cancer (CC) was considered to be the most common gynaecological cancer, with an estimated 342,000 deaths worldwide each year, as the majority of patients were diagnosed at an advanced stage of the disease. The purpose of this study was to evaluate the predictive value of multi-locus methylation assay for the early detection of CC. The cervical exfoliated cell samples from 492 HPV-positive females with cervical lesions were collected and subjected to methylation detection of gene FAM19A4, EPB41L3 and PAX1 after bisulfite conversion. The levels of gene methylation in patients with different severity of cervical lesions were evaluated and compared. The receiver-operating characteristic (ROC) curve was established and efficacy indexes such as sensitivity, specificity and area under the curve (AUC) were calculated to assess the diagnostic value of DNA methylation detection at multiple gene loci for CC. The methylation levels of FAM19A4, EPB41L3 and PAX1 were significantly increased with the grade of cervical squamous intraepithelial lesions. The sensitivities of FAM19A4, EPB41L3 and PAX1 alone for high-grade squamous intraepithelial lesion (HSIL) and CC diagnosis were 84.6%, 86.3% and 88.0%, respectively; when three markers were combined by a logistic regression model, the sensitivity was 88.0%, with a high specificity of 97.7% and AUC of 0.957 (95% CI 0.937-0.977). Methylation status of FAM19A4, EPB41L3 and PAX1 were highly specific and effective for monitoring the progression of cervical lesions and the tri-gene methylation assay could be used as a triage tool for CC early screening., (© 2024. The Author(s).)

Objective: To preliminarily investigate the clinical outcomes of secondary loop electrosurgical excision procedure (LEEP) combined with transcervical resection of endocervical tissue (i.e., second combined surgeries) in patients with positive endocervical margins following the initial LEEP for high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS) of the cervix. Methods: Patients who underwent second combined surgeries due to positive endocervical margins after the initial LEEP for cervical HSIL or AIS at Obstetrics and Gynecology Hospital, Fudan University between August 2015 and September 2023 were included. Postoperative cytological examinations, high-risk human papillomavirus (HR-HPV) testing, colposcopic biopsy results, and cervical canal length were followed up to evaluate the clinical efficacy of second combined surgeries. Results: (1) General clinical data: a total of 67 patients were enrolled, including 34 with cervical HSIL (HSIL group) and 33 with AIS (AIS group). In the HSIL group before the time of initial LEEP, the mean age was (41.3±5.3) years, with all patients positive for HR-HPV preoperatively. Preoperative cytology results revealed ≤low-grade squamous intraepithelial lesion (LSIL) in 13 cases and ≥HSIL in 21 cases. The preoperative cervical canal length was (3.71±0.17) cm. Patients in the AIS group before their the first LEEP were at an average age of (39.1±8.7) years old, with preoperative HR-HPV positive. Among them, 16 cases showed preoperative cytological results of ≤LSIL, while 17 cases showed ≥HSIL. The preoperative cervical canal length was (3.64±0.21) cm. (2) Pathological findings and postoperative follow-up of the HSIL group following second combined surgeries:in the HSIL group, the residual rate of HSIL in the endocervical canal tissue (ECT) was 24% (8/34). Out of the 34 HSIL patients, 10 cases (29%, 10/34) remained with positive endocervical margins post-second combined surgeries. Among these 10 patients, 5 cases (5/10) had no lesion detected in ECT, while the remaining 5 cases (5/10) exhibited HSIL in their ECT. Conversely, 24 patients (71%, 24/34) had negative endocervical margins after second combined surgeries. Of these 24 patients, 3 cases (12%, 3/24) were found to have HSIL in ECT, and 21 cases (88%, 21/24) had no lesion in ECT. During follow-ups conducted at 6 and 12 months post-second combined surgeries, the clearance rates of HR-HPV were 91% (31/34) and 100% (34/34), respectively. Notably, among the 29 patients (85%, 29/34) who were followed up for a period of 2 years or longer, all cases maintained a consistently negative HR-HPV status, highlighting the effectiveness of second combined surgeries in achieving long-term HR-HPV clearance (100%, 29/29). (3) Pathological findings and postoperative follow-up of the AIS group following second combined surgeries: the residual rate of AIS in the ECT following second combined surgeries among AIS patients was 15% (5/33). Out of the 33 AIS patients, 11 cases (33%, 11/33) had positive endocervical margins post-operation, among whom AIS was detected in the ECT of 2 cases (2/11), while 1 case (1/11) was diagnosed with adenocarcinoma in the cervical canal tissue (subsequently underwent radical surgery and was excluded from this study). In contrast, 22 patients (67%, 22/33) had negative endocervical margins post-operation, with AIS found in the ECT of 2 cases (9%, 2/22) and no lesions detected in the remaining 20 cases (91%, 20/22). Follow-up evaluations conducted at 6 and 12 months postoperatively revealed HR-HPV clearance rates of 91% (29/32) and 97% (31/32), respectively. All 32 (100%, 32/32) AIS patients were followed up for a duration of ≥2 years post-second combined surgeries, during which HR-HPV remained consistently negative. (4) Complications and cervical length following second combined surgeries: neither the HSIL group nor the AIS group experienced significant complications such as hemorrhage, infection or cervical canal adhesion. At the 6-month follow-up, the cervical length of both HSIL and AIS patients exceeded 3 cm. By the 12-month follow-up, the cervical length had recovered to 96.5% and 97.5% when compared to the original length, respectively, for the HSIL and AIS groups. Conclusions: For patients with HSIL or AIS who exhibit positive endocervical margins following the initial LEEP procedure, undergoing second combined surgeries presents as an optimal choice. This surgical intervention guarantees thorough excision of the lesion, and subsequent colposcopic follow-up evaluations consistently demonstrate an absence of residual disease or recurrence. Moreover, it augments the rate of sustained HR-HPV negativity, thereby contributing to more favorable clinical outcomes.

The development of cervical and vaginal intraepithelial neoplasias (CIN and VaIN) is strongly associated with human papillomavirus (HPV) infections, representing key precancerous conditions in women. This study investigates the influence of different cervical treatment methods on the rate of subsequent vaginal neoplasia. It also considers age and menopausal status as risk factors for higher-grade VaIN and the role of persistent HPV infections in the development of new VaIN cases post-treatment. The cohort consisted of 275 female patients treated for CIN, with a follow-up period of six months including HPV and ThinPrep cytologic test (TCT) testing. The evaluated treatments included laser therapy, cervical conization, loop electrosurgical excision procedure (LEEP), and radical hysterectomy. Statistical analysis was performed using SPSS 26.0 to determine treatment efficacy, the impact of age and menopausal status, and the relationship between HPV clearance and VaIN outcomes. Radical hysterectomy was linked with a higher recurrence of VaIN. Additionally, patients over 50 years old and those who were postmenopausal were significantly more likely to develop more severe VaIN and persistent HPV infections. Persistence of HPV after treatment was linked to a higher incidence of new VaIN cases. High-risk HPV significantly increased the recurrence of VaIN, with no significant link found between TCT results and VaIN severity. Therefore, selecting appropriate cervical lesion treatment, considering the patient's age and menopausal status, and managing HPV infections are essential in preventing and managing the risk and progression of VaIN. Radical hysterectomy showed a distinct increase in VaIN incidence, emphasizing the need for individualized clinical assessments.

Background: Cervical cancer remains a public health problem despite heavy global investment in health systems especially in low-and-middle-income countries (LMIC). Prophylactic vaccines against the most commonly detected human papillomavirus (HPV) types in cervical cancers are available and decisions on the selection of vaccine design depends on the prevalence of high-risk (hr) HPV genotypes for a particular region. In 2015, Botswana adopted the use of a quadrivalent HPV vaccine as a primary prevention strategy. Secondary prevention includes cervical smear screening whose uptake remains notably low among indigenous and marginalized communities despite efforts to improve access., Aim: To determine the prevalence of hrHPV genotypes and cervical lesions' burden in women from the indigenous and marginalized communities of Botswana., Methods: This prospective survey enrolled 171 non-HPV vaccinated women aged 21 years and older. Face-to-face interviews, Pap smear screening, hr-HPV and Human Immuno-deficiency virus (HIV) testing were carried out. Conventional Papanicolau smears were analyzed and cervical brushes were preserved for hrHPV testing using the Ampfire Multiplex HR-HPV protocol which detects the following genotypes: HPV 16, 18, 31, 35, 39, 45, 51, 52, 53, 56, 58, 59 and 68., Results: In this study, 168/171 (98.6%) of the women consented to HIV testing; 53/171 (31%) were living with HIV and self-reported enrolment on antiretroviral therapy. Among the women examined, 23/171 (13.5%) had cervical dysplasia with most presenting with Atypical Squamous Cells of Undetermined Significance 8/23 (35%), Low-Grade Squamous Intraepithelial Lesions 8/23 (35%), Atypical Squamous Cells-High Grade 4/23 (17%), Atypical Endocervical Cells 2/23 (9%) and Atypical Endocervical Cell favoring neoplasia 1/23(4%). However, no High-Grade Squamous Intraepithelial Lesions (HSIL) or squamous cell carcinoma (SCC) were detected. Overall hrHPV prevalence in this study was at 56/171 (32.7%). The most commonly detected hrHPV genotypes in women with cervical dysplasia were HPV39 (6.25%), HPV51 (14.5%), HPV52 (12.5%) and HPV56 (4%). Notably, HPV 16 and 18 were not found in women with cervical dysplasia., Conclusions: Our study provides valuable insights into the prevalence and distribution of hrHPV genotypes in indigenous and marginalized communities in Botswana, and the need for further investigation of their potential role in cervical carcinogenesis in this population. These results may also serve as baseline data to facilitate future evaluation of the HPV vaccine needs., (© 2024. The Author(s).)

Objectives: To investigate optical coherence microscopy (OCM) imaging features and the application value of these high-resolution images for identifying endocervical canal lesions (ECLs), which is a clinical dilemma in cervical cancer screening programs., Methods: In total, 520 OCM images were obtained by scanning the cervical canal lesions with an ultra-high-resolution OCM system (204 specimens from 73 patients). The OCM morphologic characteristics of ECLs were observed and summarized, and then 3 researchers performed a diagnostic test of OCM images of cervical canal lesions. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, 95% confidence interval of each parameter, and interinvestigator agreement (κ) were calculated., Results: Normal endocervix, cysts, squamous metaplasia, high-grade squamous intraepithelial lesions involving glands, and invasive carcinoma had distinct OCM characteristics, which correlated well with corresponding H&E histologic sections. The accuracy, sensitivity, and specificity of the 3 researchers were 90.6%, 89.3% (95% CI, 86.5%-91.7%) and 91.6% (95% CI, 89.2%-93.5%), respectively. The positive predictive value was 90.1% (95% CI, 87.3%-92.4%), and the negative predictive value was 90.9% (95% CI, 88.5%-92.9%), with almost perfect agreement (κ = 0.874)., Conclusions: The application of the OCM system in cervical canal lesions is feasible and could help improve detection of occult ECLs in cervical cancer screening programs. This study lays the foundation for further research on OCM in cervical canal lesions in vivo, which also has a potential impact on projecting pathologic evaluation beyond what is currently possible, perhaps globally., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To assess the association of demographic and clinical features of patients with clinicopathological markers in cases of abnormal Pap smear., Methods: The retrospective study was conducted from July 2020 to June 2021 at Al-Elwiya Maternity Teaching Hospital, Baghdad, Iraq, and comprised data from January 2019 to June 2020 of women who underwent Pap-smear. Data was retrieved for patients' age, marital status, smoking status, clinical symptoms at presentation, findings of clinical and cytological examinations, as well as follow-up or human papillomavirus testing data where applicable. Data was analysed using SPSS 26., Results: Of the 560 women with mean age 40.42±10.211 years, 26(4.6%) were attending the hospital for routine check-ups/screening, and 12(2.1%) for follow-up screening with previous abnormal Pap-tests, while the rest had been referred for medical consultation. The most common diagnosis was negative for intraepithelial lesion or malignancy 403(72%) Cervical epithelial abnormalities were seen in 136(24.3%) cases, and, of them, 12(8.8%) returned for follow-up. Epithelial abnormalities had a significant association with age, clinical presentation, and clinical examination results (p<0.05), while it had a non-significant relation with marital and smoking statuses (p>0.05)., Conclusions: The majority of subjects were referred cases, with routine cervical screening being <5%. Increasing public awareness about the importance of cervical screening and follow-up is essential.

The concordance rate between conization and colposcopy-directed biopsy (CDB) proven cervical high-grade squamous intraepithelial lesion (HSIL) were 64-85%. We aimed to identify the risk factors associated with pathological upgrading or downgrading after conization in patients with cervical HSIL and to provide risk-stratified management based on a machine learning predictive model. This retrospective study included patients who visited the Obstetrics and Gynecology Hospital of Fudan University from January 1 to December 31, 2019, were diagnosed with cervical HSIL by CDB, and subsequently underwent conization. A wide variety of data were collected from the medical records, including demographic data, laboratory findings, colposcopy descriptions, and pathological results. The patients were categorized into three groups according to their postconization pathological results: low-grade squamous intraepithelial lesion (LSIL) or below (downgrading group), HSIL (HSIL group), and cervical cancer (upgrading group). Univariate and multivariate analyses were performed to identify the independent risk factors for pathological changes in patients with cervical HSIL. Machine learning prediction models were established, evaluated, and subsequently verified using external testing data. In total, 1585 patients were included, of whom 65 (4.1%) were upgraded to cervical cancer after conization, 1147 (72.4%) remained having HSIL, and 373 (23.5%) were downgraded to LSIL or below. Multivariate analysis showed a 2% decrease in the incidence of pathological downgrade for each additional year of age and a 1% increase in lesion size. Patients with cytology > LSIL (odds ratio [OR] = 0.33; 95% confidence interval [CI], 0.21-0.52), human papillomavirus (HPV) infection (OR = 0.33; 95% CI, 0.14-0.81), HPV 33 infection (OR = 0.37; 95% CI, 0.18-0.78), coarse punctate vessels on colposcopy examination (OR = 0.14; 95% CI, 0.06-0.32), HSIL lesions in the endocervical canal (OR = 0.48; 95% CI, 0.30-0.76), and HSIL impression (OR = 0.02; 95% CI, 0.01-0.03) were less likely to experience pathological downgrading after conization than their counterparts. The independent risk factors for pathological upgrading to cervical cancer after conization included the following: age (OR = 1.08; 95% CI, 1.04-1.12), HPV 16 infection (OR = 4.07; 95% CI, 1.70-9.78), the presence of coarse punctate vessels during colposcopy examination (OR = 2.21; 95% CI, 1.08-4.50), atypical vessels (OR = 6.87; 95% CI, 2.81-16.83), and HSIL lesions in the endocervical canal (OR = 2.91; 95% CI, 1.46-5.77). Among the six machine learning prediction models, the back propagation (BP) neural network model demonstrated the highest and most uniform predictive performance in the downgrading, HSIL, and upgrading groups, with areas under the curve (AUCs) of 0.90, 0.84, and 0.69; sensitivities of 0.74, 0.84, and 0.42; specificities of 0.90, 0.71, and 0.95; and accuracies of 0.74, 0.84, and 0.95, respectively. In the external testing set, the BP neural network model showed a higher predictive performance than the logistic regression model, with an overall AUC of 0.91. Therefore, a web-based prediction tool was developed in this study. BP neural network prediction model has excellent predictive performance and can be used for the risk stratification of patients with CDB-diagnosed HSIL., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Objective: This study aims to analyse high-grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020., Methods: This study included 305,940 asymptomatic women aged 25-65 years. The eligible population was invited to undergo a screening cervico-uterine-smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix., Results: Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25-29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high-grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC-H) smears., Conclusion: In the study population, the prevalence of LIEHG was high in women under 35 years. Low-grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow-up of LSIL and ASC-US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Computer-assisted screening (CAS) shows equal performance compared to manual screening, although results are heterogeneous. Furthermore, using CAS may save costs through a potentially increased screening productivity of technicians, therefore also offering a solution for temporary and structural capacity shortage. We evaluated the circumstances under which CAS will be cost-effective compared to manual cytology triage in a primary HPV-based cervical screening programme., Methods: Microsimulation model MISCAN-Cervix was used to evaluate 198 different CAS scenarios with varying probabilities to detect cervical intraepithelial neoplasia grade 1 (CIN1) and CIN3 and cost reductions per test, compared to manual cytology triage. Cost-effectiveness was evaluated by costs per (quality-adjusted) life year ((QA)LY) gained., Results: CAS will be cost-effective in all scenarios, except for the following combinations: (1) no cost reduction and an increased probability of detecting CIN1, (2) a cost reduction of €2 per test and an increased probability of detecting CIN1 from 4% onwards or (3) a cost reduction of €4 per test and an increased probability of detecting CIN1 from 6% onwards, compared to manual cytology triage. All CAS scenarios with any reduction in the probability of detecting CIN1 (i.e., increased CIN2+ specificity), or a reduction in costs from €6 per test onwards suggested a more cost-effective strategy compared to manual cytology triage., Conclusion: As we based our analysis on a realistic range in costs and test performance, the implementation of CAS is likely to be cost-effective. Our results can be used as a guideline to advise when to choose CAS instead of manual cytology triage., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Uterine-sparing surgery for pelvic organ prolapse (POP) repair has shown good results, but the potential negative implications of leaving the uterus in place are yet to be fully defined. We aimed to assess the risk of unanticipated abnormal gynecological pathology at the time of reconstructive pelvic surgery. Methods: A retrospective consecutive case series including women who underwent vaginal hysterectomy for POP repair at a tertiary medical center in 2006-2020. All patients were offered a free Pap smear test at the age of 65 years as part of a national screening program. Transvaginal ultrasound was routinely performed preoperatively. Standard 3 pedicle hysterectomy was performed with/without bilateral salpingo-oophorectomy (BSO). Results: The study comprised 462 women of mean age 63 ± 9.3 years without previous known malignant or premalignant pathology. Benign pathology was observed in 286 patients (61.9%). Endometrial malignancy was found in three patients (0.7%) and significant premalignant pathology in 15 patients (3.2%), including cervical intraepithelial neoplasia stage 2-3 in seven patients (1.5%) and complex hyperplasia with atypia in eight patients (1.7%). All these pathologies were found in postmenopausal women. None had preoperative clinical symptoms or endometrial thickness of ≥5 mm on preoperative ultrasound. In the 35 patients after BSO, adnexal findings were normal (77.2%) or benign (22.8%). Conclusions: Premenopausal women with uterovaginal prolapse and normal preoperative evaluation have a minimal risk of significant abnormal uterine pathology. In postmenopausal women, the risk of unanticipated malignant uterine pathology is 0.7% and 3.2% for significant premalignancy.

Purpose: Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain., Methods: A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2 years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H 2 O 2 ), β-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1., Results: Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H 2 O 2 (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8 months, and then stabilizing., Conclusion: Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia., (© 2024 UICC.)

Background: The risk of cervical cancer progression in high-risk human papillomavirus (HR-HPV)-positive women is associated with cervical lesion severity and molecular heterogeneity. Classification systems based on p16 and Ki67 expression cumulative scores (0-3 each)-p16/Ki67 collectively known as an immunoscore [IS]-are an accurate and reproducible method for grading cervical intraepithelial neoplasia (CIN) lesions. Meanwhile, DNA methylation is an early event in the development of cervical cancer. Hence, this study evaluated the relationship among CIN, p16/Ki-67 IS, and PAX1/ZNF582 methylation., Methods: In this study, 414 HPV-positive paraffin-embedded specimens were collected, and PAX1/ZNF582 methylation and the p16/ki67 IS were determined. A total of 43 invalid samples were excluded and 371 were included in the statistical analyses. There were 103 cervicitis, 95 CIN1, 71 CIN2, 89 CIN3, and 13 squamous cell carcinoma (SCC) cases. The association between PAX1/ZNF582 methylation and p16/Ki6 immunohistochemical staining scores was analyzed., Results: The ΔCp of PAX1 m (PAX1 methylation) and ZNF582 m (ZNF582 methylation) decreased with cervical lesion severity (Cuzick trend test, all P < 0.001). The severity of the cervical lesions and p16, Ki67, and p16/Ki67 IS showed an increasing trend (Multinomial Cochran-Armitage trend test, all P < 0.001). The prevalence of PAX1 m /ZNF582 m increased with an increase in the IS of p16, Ki67, and p16/Ki67 (Cochran-Armitage trend test, all P < 0.001). In cervical SCC, the IS was 5-6, and the PAX1 m /ZNF582 m was positive. Meanwhile, heterogeneity was observed in CIN lesions: 10 cases had an IS of 3-4 and were PAX1 m /ZNF582 m -positive in ≤ CIN1; 1 case had an IS of 0-2 and was PAX1 m /ZNF582 m -positive in CIN2/3., Conclusions: Significant heterogeneity was observed in CIN lesions for p16 and Ki67 immunohistochemical staining scores and PAX1/ZNF582 methylation. This may help clinicians personalize the management of CIN based on the predicted short-term risk of cancer progression, minimizing the rate of missed CIN1 diagnoses and incorrect treatment of CIN2/3., (© 2024. The Author(s).)

Invasive cervical cancers (ICC), caused by HPV infections, have a heterogeneous molecular landscape. We investigate the detection, timing, and HPV type specificity of somatic mutations in 3929 HPV-positive exfoliated cervical cell samples from individuals undergoing cervical screening in the U.S. using deep targeted sequencing in ICC cases, precancers, and HPV-positive controls. We discover a subset of hotspot mutations rare in controls (2.6%) but significantly more prevalent in precancers, particularly glandular precancer lesions (10.2%), and cancers (25.7%), supporting their involvement in ICC carcinogenesis. Hotspot mutations differ by HPV type, and HPV18/45-positive ICC are more likely to have multiple hotspot mutations compared to HPV16-positive ICC. The proportion of cells containing hotspot mutations is higher (i.e., higher variant allele fraction) in ICC and mutations are detectable up to 6 years prior to cancer diagnosis. Our findings demonstrate the feasibility of using exfoliated cervical cells for detection of somatic mutations as potential diagnostic biomarkers., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

To compare the clearance rate of high-risk human papillomavirus (HR-HPV) in patients with high-grade squamous intraepithelial lesion (HSIL) after 2 different treatments (conization vs hysterectomy), and investigate the influencing factors. A retrospective cohort was established in HSIL patients with HR-HPV infection treated with conization or hysterectomy from July 2020 to May 2022. Age matching (1:1) was conducted between conization group and hysterectomy group. Chi-square test and t-test were employed to compare baseline and clinical characteristics between the 2 groups (conization vs hysterectomy). In addition, univariate and multivariate logistic regression analyses were conducted to compare the influencing factors for HR-HPV clearance at 6 months after surgery. The HR-HPV clearance rates at 6 months were 70.6% and 73.8% in conization group and hysterectomy group in the matched groups, respectively (P = .755). Similarly, at 12 months, the clearance rates were 78.6% and 76.5% in the matched groups, respectively (P = .844). Considering different age groups among all patients, the HR-HPV clearance rates were 81.8%, 72.9%, 73.5%, and 53.6% in the 20 to 30-year, 31 to 40-year, 41 to 50-year and 51 to 60-year groups at 6 months, respectively, and the clearance rates were 87.5%, 80.6%, 84.5% and 52.9% at 12 months, respectively. For HSIL, the postoperative HPV clearance rates were similar between the 2 groups (conization vs hysterectomy), conization is enough to resect the lesion and eliminate HPV. In addition, we should pay attention to the postoperative HR-HPV status in the older population of the 2 groups., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To investigate the high-risk factors associated with concurrent cervical intra-epithelial neoplasia (CIN) and vaginal intra-epithelial neoplasia (VaIN) in patients with high-grade lesions., Methods: This retrospective study at the Obstetrics and Gynecology Hospital of Fudan University included patients diagnosed with concurrent CIN2/3 and VaIN2/3 (concurrent group) over the period from January 1, 2019, to December 31, 2019. Patients with only CIN2/3 during the corresponding period were selected chronologically on a 1:2 basis (CIN group). Demographic data, human papillomavirus (HPV) infection rates, genotypes, and cytology results were compared between the groups., Results: A total of 128 patients were included. The median age in the concurrent group was 50 years (range 20-79), which was significantly higher than the median age of 38 (range 23-72) in the CIN group (p<0.001). The cytological sensitivity for identifying high-grade lesions was markedly higher in the concurrent group at 83.1% (103 out of 124) compared with 68.4% (175 out of 256) in the CIN-only group (p=0.002). The prevalence of HPV 16 was 62.8% in the concurrent group, significantly higher than 51.6% in the CIN group (p=0.04)., Conclusions: The risk of concurrent VaIN2/3 increases with age among women with CIN2/3. Cytology screening is effective for detecting concurrent VaIN2/3, with a sensitivity of 83.1%., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Null.

Introduction: Active surveillance for cervical intraepithelial neoplasia grade 2 (CIN2) has been implemented recently in many countries, including the Nordic countries. In Denmark, the only eligibility criterion for active surveillance for CIN2 is that the woman should be of reproductive age. With this study, we aimed to evaluate clinical and socioeconomic characteristics in women with CIN2 managed by active surveillance or large loop excision of the transformation zone (LLETZ) and to evaluate temporal changes in the clinical management of CIN2., Material and Methods: We conducted a Danish nationwide study using data from healthcare registries. All female residents aged 18-40 years, diagnosed with incident CIN2 from January 1, 1998, to February 29, 2020, were included. We collected data on age, index cytology result, year of CIN2 diagnosis, region of residence, civil status, HPV vaccination status, and socioeconomic position indicators. The variables were tabulated overall and by management group (active surveillance vs. LLETZ). To evaluate time trends, we used joinpoint regression to calculate the annual percentage change (APC), including 95% confidence intervals (CI)., Results: Of the 27 536 women with CIN2 included, 12 500 (45.4%) underwent active surveillance, and 15 036 (54.6%) underwent a LLETZ. Women undergoing active surveillance were younger, more often HPV-vaccinated, and more likely to have a normal/low-grade index cytology result than women undergoing LLETZ. Socioeconomic position indicators did not differ. Over time, the proportion of women undergoing active surveillance increased from 21.7% in 2004 to 73.6% in 2019 (APC 9.7, 95% CI 8.1-11.4). The proportion of women undergoing active surveillance aged <30 declined over time (APC -2.2, 95% CI -2.9 to -1.5). The proportion of women with normal/low-grade index cytology increased slightly to 51.6% in 2019 (APC 0.8, 95% CI 0.4-1.3)., Conclusions: The use of active surveillance for CIN2 has increased over the past two decades in Denmark. Observed differences in characteristics between women undergoing active surveillance vs LLETZ are likely related to indications for clinical management., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: Early detection and treatment of cervical precancers can prevent disease progression. However, in low-resource communities with a high incidence of cervical cancer, high equipment costs and a shortage of specialists hinder preventative strategies. This manuscript presents a low-cost multiscale in vivo optical imaging system coupled with a computer-aided diagnostic system that could enable accurate, real-time diagnosis of high-grade cervical precancers., Methods: The system combines portable colposcopy and high-resolution endomicroscopy (HRME) to acquire spatially registered widefield and microscopy videos. A multiscale imaging fusion network (MSFN) was developed to identify cervical intraepithelial neoplasia grade 2 or more severe (CIN 2+). The MSFN automatically identifies and segments the ectocervix and lesions from colposcopy images, extracts nuclear morphology features from HRME videos, and integrates the colposcopy and HRME information., Results: With a threshold value set to achieve sensitivity equal to clinical impression (0.98 [p = 1.0]), the MSFN achieved a significantly higher specificity than clinical impression (0.75 vs. 0.43, p = 0.000006)., Conclusion: Our findings show that multiscale optical imaging of the cervix allows the highly sensitive and specific detection of high-grade precancers., Significance: The multiscale imaging system and MSFN could facilitate the accurate, real-time diagnosis of cervical precancers in low-resource settings.

Full-thickness high-grade squamous intraepithelial lesions (HSIL) are precursors of invasive cervical squamous cell carcinoma (SCC). The World Health Organization and Lower Anogenital Squamous Terminology Standardization Project for human papilloma virus (HPV)-associated lesions divide full-thickness HSIL of the cervix into thin HSIL with thickness of 1 to 9 cell layers and the typical full-thickness HSIL of >10 cell layers. Although HPV oncogene transcripts and p16ink4a overexpression, as markers of transforming HPV infection, are detectable in thin HSIL, the biological significance of thin HSIL in cervical carcinogenesis remains poorly understood. To further characterize thin HSIL, we performed a comparative study of chromosomal copy number variations (CNV), an analysis of dysregulated genes present in the segments with CNV, and a generalized genetic complexity calculation for 31 thin HSIL, 31 thick HSIL, 24 microinvasive SCC (pT1a SCC), and 22 highly invasive SCC samples. Thin HSIL share various CNV and specific dysregulated gene pathways with thick HSIL and invasive SCC. Thin HSIL exhibited an average CNV of 11.6% compared with 14.1% for thick HSIL, 15.5% for pT1a SCC, and 26.6% for highly invasive SCC. The CNV included gains at 1q and 3q (40% and 43%, respectively), partial loss of 3p, and loss of chromosomes 11 (18%), 16 (50%), 20 (35%), and 22 (40%). Pathways affected solely in thin HSIL were those enhancing immune evasion and primarily involved the (interleukin) IL6, IL21, and IL23 genes. ILs are transiently upregulated in response to infection and play a crucial role in mounting antitumor T-cell activity. Deregulation reflects an attempt by the HPV to evade the initial immune response of the host. The primary pathways shared by thick HSIL and invasive SCC were interactions between lymphoid and nonlymphoid cells, NOTCH2 signaling, tight junction interactions (primarily of the claudin family), and FGR2 alternative splicing. Our results show that thin HSIL carry similar genetic changes as thick HSIL and SCC, indicating that thin HSIL are true precursor lesions that can progress to thick HSIL and SCC., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cervical cancer is the fourth most common malignancy in women worldwide. The identification of human papillomavirus (HPV) as the main etiologic cause of cervical cancer has led to the development and adaptation of HPV molecular diagnostics as a cervical cancer screening and prevention tool. This article highlights six Food and Drug Administration-approved HPV molecular platforms, each with unique advantages and disadvantages. In addition, HPV vaccination and the emergence of HPV self-collection as an alternative testing strategy are discussed., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The finding of atypical glandular cells (AGC) on Papanicolaou test is becoming more important as the incidence of squamous intraepithelial lesions decreases in recent decades. Therefore, the interpretation and follow-up of patients with AGC are particularly important. The aim of our study was to assess the histologic findings and clinical correlations in patients with AGC identified on Papanicolaou test., Materials and Methods: A total of 714 patients with AGC identified on cervical Papanicolaou tests were studied for their clinicopathologic features, such as follow-up histology and patient age. We investigated the histologic follow-up results for each individual subcategories of AGC and their correlation with patients' age., Results: Most of the glandular cell abnormalities (80.0%) in the study group were classified as "atypical glandular cells, not otherwise specified (NOS)". About 28.9% of patients' follow-up histology showed malignant or precancerous lesions. The mean age of patients with malignant or precancerous lesions was significantly higher than that of patients with benign or non-precancerous lesions. The malignant histologies included 52 cases of endometrial cancers and 31 cases of cervical carcinomas. The second most common subcategory was "atypical glandular cells, favor neoplastic" (5.0%), while "atypical endocervical cells, favor neoplastic" constituted about 2.7% of cases in our study. The average age of patients with "atypical glandular cells, favor neoplastic" was significantly higher than that of patients with "atypical endocervical cells, favor neoplastic". The follow-up histology of about 82.1% of "atypical glandular cells, favor neoplastic" showed endometrial (73.9%) or cervical malignancies (26.1%). The follow-up histology of about 70.6% of "atypical endocervical cells, favor neoplastic" showed endometrial (50.0%) or cervical cancers (50.0%). Other glandular abnormalities included 25 of 714 cases of "atypical endometrial cells" (3.5%) and 6 of 714 cases of "atypical endocervical cells" (0.8%)., Conclusion: Based on our data, we have observed significantly more endometrial malignancies in both "atypical glandular cells, NOS" and "atypical glandular cells, favor neoplastic" subcategories and even some in "atypical endocervical cells, favor neoplastic" category. This predominance of endometrial malignancies is also associated with patients' age and tumor types., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Perinatal care provides important health care opportunities for many individuals at risk for cervical cancer. Pregnancy does not alter cervical cancer screening regimens. ASCCP risk-based management has a colposcopy threshold of a 4% immediate risk of cervical intraepithelial neoplasia (CIN) 3 or cancer, but the actual risk can be considerably higher based on current and past screening results. Improving cervical cancer outcomes with diagnosis during pregnancy rather than postpartum and facilitating further evaluation and treatment postpartum for lesser lesions are the perinatal management goals. Although colposcopy indications are unchanged in pregnancy, some individuals with lower risk of CIN 2-3 and reliable access to postpartum evaluation may defer colposcopy until after delivery. Cervical intraepithelial neoplasia diagnosed in pregnancy tends to be stable, with frequent regression postpartum, though this is not universal. Colposcopic inspection during pregnancy can be challenging. Although biopsies in pregnancy are subjectively associated with increased bleeding, they do not increase complications. Endocervical curettage and expedited treatment are unacceptable. Treatment of CIN 2-3 in pregnancy is not recommended. Excisional biopsies in pregnancy are reserved for suspicion of malignancy that cannot be confirmed by colposcopic biopsy and when excisional biopsy results would alter oncologic or pregnancy care. Surveillance of high-grade lesions in pregnancy uses human papillomavirus-based testing, cytology, and colposcopy, with biopsy of worsening lesions every 12-24 weeks from diagnosis until postpartum evaluation. Mode of delivery does not definitively affect persistence of CIN postpartum. Postpartum care may involve a full colposcopic evaluation or expedited excisional procedure if indicated., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Cervical cancer which is caused by persistent infection with oncogenic human papillomavirus (HPV), is the third most common cancer. HPV infection causes the progression of the normal cervix to cervical intraepithelial neoplasia (CIN) because it often occurs at the function conversion of the cervical squamous epithelium and columnar epithelium zone, further to invasive carcinoma. The difference in the ALDH1 expression was very significant. With the progression of cervical cancer, reports explained obviously increased nuclear and cytoplasm ALDH1 staining in comparisons of cervical carcinomas and normal cervix (P < 0.0001), cervical carcinomas compared with CIN (P = 0.0002). Therefore, ALDH1 as a stem marker, not only resists cervical cancer but also resists in normal cervix and CIN tissues. Developing an experimental method to discover cervical cancer earlier is feasible. Furthermore, the ALDH1 was expressed in human cervical cancer cell lines (Hela, SiHa, CaSki, HT-3, and C33A) together with western blot and immunocytochemical analysis. ALDH1 plays a significant role in nuclear and cytoplasm staining by immunochemistry in single or clustered HT-3 and C33A cells. However, western blot and immunochemical analysis did not detect ALDH1 in HeLa or CaSki, SiHa cells. We also discovered that there were no remarkable differences in age, tumor size, clinical TNM staging, multiple pelvic lymph node metastasis, or histological staging (p > 0.05) between the ALDH1-positive groups in 100 cervical cancer tissues. But after the control variable age, different ALDH rating survival function contrasted, it can be concluded that the higher ALDH1 scores with the survival of patients with the worse condition.

Persistent human papillomavirus HPV infection is a necessary but insufficient condition for cervical cancer. Microorganisms are crucial environmental factors in cancers susceptibility and progression, recently attracting considerable attention. This study aimed to determine the infection status and relationship between high-risk HPV (HR-HPV) and lower genital tract infectious pathogens in cervical cancer and its precursors. From a retrospective and a prospective cohort analysis, Escherichia coli ( E. coli ) dominated the pathogens isolated from cervical discharges, and an isolation rate uptrend has been shown recently. HPV16 and E. coli 's coinfection rate gradually increased with the severity of cervical intraepithelial neoplasia. The adhesion and invasion abilities of the isolated E. coli to HPV16-positive SiHa cells were evaluated in vitro . The TCGA database and cervical tissues samples analysis showed that IL-10 was upregulated in cervical cancer. IL-10 expression levels increased in tissue samples with the severity of cervical cancer and its precursors with HPV16 and E. coli coinfection. Although no significant changes in IL-10 production were observed in the co-culture supernatant, we hypothesized that Treg immune cells in the tumour microenvironment might be responsible for the local IL-10 upregulation, according to our data showing Foxp3 upregulation and an upward trend with the cervical intraepithelial neoplasia grading to cancer and tumours with E. coli and HPV16 coinfection. Our data provide insights into the possible role of E. coli in cervical cancer progression and suggest that the application of HPV and E. coli screening programs may be an effective strategy to relieve the burden of cervical cancer and its precursor lesions.

Background: Cervical cancer often originates from cervical cell dysplasia. Previous studies mainly focused on surgical margins and high-risk human papillomavirus persistence as factors predicting recurrence. New research highlights the significance of positive findings from endocervical curettage (ECC) during excision treatment. However, the combined influence of surgical margin and ECC status on dysplasia recurrence risk has not been investigated., Methods: In this retrospective study, data from 404 women with high-grade squamous intraepithelial lesions (HSIL) who underwent large loop excision of the transformation zone (LLETZ) were analyzed. Records were obtained retrospectively from the hospital's patient database including information about histopathological finding from ECC, endocervical margin status with orientation of residual disease after LLETZ, recurrent/persistent dysplasia after surgical treatment and need for repeated surgery (LLETZ or hysterectomy)., Results: Patients with cranial (= endocervical) R1-resection together with cells of HSIL in the ECC experienced re-surgery 17 times. With statistical normal distribution, this would have been expected to happen 5 times (p < 0.001). The Fisher's exact test confirmed a statistically significant connection between the resection status together with the result of the ECC and the reoccurrence of dysplasia after surgery (p < 0,001). 40,6% of the patients with re-dysplasia after primary LLETZ had shown cranial R1-resection together with cells of HSIL in the ECC. Investigating the risk for a future abnormal Pap smear, patients with cranial R1-resection together with dysplastic cells in the ECC showed the greatest deviation of statistical normal distribution with SR = 2.6., Conclusion: Our results demonstrate that the future risk of re-dysplasia, re-surgery, and abnormal Pap smear for patients after LLETZ due to HSIL is highest within patients who were diagnosed with cranial (endocervical) R1-resection and with cells of HSIL in the ECC in their primary LLETZ. Consequently, the identification of patients, who could benefit of intensified observation or required intervention could be improved., (© 2024. The Author(s).)

Background: It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region., Methods: A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results., Results: The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063-7.342) and HPV33 (OR = 4.361; 95% CI 2.307-8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579-3.787), HPV51 (OR = 1.651; 95% CI 1.086-2.510) and HPV58(OR = 1.661; 95% CI 1.166-2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101-3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329-4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127-2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes., Conclusion: HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region., (© 2024. The Author(s).)

Background: Nitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia., Methods: The study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction., Results: High-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5-45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2-9.8) (p = < 0.001). Patients with high-grade atypia showed significantly higher NOx levels (38.0 µmol/mL, IQR: 24.6-94.7) in comparison to NILM and low-grade atypia cases (5.0 µmol/mL, IQR: 1.6-33.3 and 34.5 µmol/mL, IQR: 11.7-61.7, respectively) (p = 0.006). Although the NOx levels among hrHPV-positive cases with low-grade atypia (40.4 µmol/mL, IQR: 33.3‒61.8) were higher than those with NILM (36.2 µmol/mL, IQR: 35.7‒44.0) and high-grade atypia (38.0 µmol/mL, IQR: 24.6‒94.7), the difference was not significant (p = 0.771). ROC curve analysis indicated that the cervical NOx cut-off values of > 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively., Conclusions: The high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes., (© 2024. The Author(s).)

Background: Human papillomavirus (HPV) screening and vaccination exert efficacy in controlling the progression of cervical cancer. Thus, examinations into HPV prevalence, age-stratified specificity, genotype distribution, and their correlation with pathological outcomes can furnish robust evidence for customizing high-quality population screening and management., Methods: A cohort of 17,923 women attending clinics in the Jintang area, Sichuan, from January 2019 through August 2023 were enrolled in the study. Genotyping of HPV was conducted using real-time polymerase chain reaction (RT-PCR). The epidemiology and the relationship between HPV infection and histologic/cytologic abnormalities were subjected to analysis., Results: HPV infection was identified in 4387 women. The outpatient group exhibited a significantly higher HPV infection rate compared to the healthy examination group (26.5% vs. 17.5%, p < 0.05). The distribution of infection rates across different age groups exhibited a U-shaped pattern, with the highest infection rate in the group ≤20 years of age, succeeded by those >60 years of age. The 31-40 age group demonstrated the lowest prevalence of infection, but upon infection, its prevalence of the precancerous lesion CIN2-3 reached a maximum of 29.0%, constituting a novel finding. The most prevalent genotype was HPV52, followed by HPV16, 58, 53, 68, and 18. In the cytologic and histologic abnormalities group, the most common types were HPV52, 16, and 58. HPV16 predominantly appeared in high-grade intraepithelial neoplasia and carcinoma in situ, constituting over 60% of cases. While HPV type 52 was not individually detected in cervical cancer cases. And some other non-vaccine-covered HPV subtypes also showed high prevalence in Sichuan. The single infection rates of NH9-HPV (high-risk HPV subtypes covered by the non-nine-valent vaccine) in CIN2-3 and cervical cancer patients were 6.5% and 2.6%, respectively. Among them, HPV51, HPV53, HPV59, and HPV35 exhibited a significant preponderance, which even higher than HPV45 and HPV31 covered by the nine-valent vaccine types. And in NL9-HPV (low-risk HPV subtypes covered by the non-nine-valent vaccine), HPV42 accounted for the highest percentage in CIN2-3. A similar decreasing trend was observed in annual infection rates in the healthy examination population and in the 31-40 and 51-60 age groups, while the ≤20 age group showed an increase. Regarding type-specificity, HPV16 and HPV58 exhibited the most rapid declines., Conclusion: This study furnishes the latest insights into the characteristics of HPV infection rate, age distribution, and genotype prevalence in Sichuan., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Vaginal atresia is a rare obstructive disease of the reproductive tract. It is characterized by the absence or underdevelopment of the vaginal canal and results in various clinical manifestations. Hysterectomy can physically and mentally burden young female patients with a congenital cervix and complete vaginal atresia. This report presents a case of type II vaginal atresia complicated by cervical dysplasia in a female patient >10 years of age. Our team opted to preserve the patient's uterus, innovated a fallopian tube transplantation technique, and performed cervicovaginal reconstruction using natural channels instead of the cervical canal. The patient experienced menarche within the first 2 weeks postoperatively, and follow-up at 6 months revealed no abnormalities.

Aims: To assess colposcopic performance and determine indicators for competency within the new Australian primary human papillomavirus (HPV) cervical screening program., Materials and Methods: A retrospective observational study of 4542 women seen at The Royal Women's Hospital Colposcopy Clinic in Melbourne, from 1 December 2017 to 31 July 2020 after a higher-risk cervical screening test (CST) result., Results: Histological CIN2+ was detected in 25.1% up to two years from first colposcopy visit (FCV). The majority (86.7%) of CIN2+ was detected early within the first six months of presentation. Biopsy rate overall was 96.1% with abnormal colposcopic impression. Of four colposcopists with a lower biopsy rate, only one was able to achieve this early detection rate. Biopsy was also taken in over 30% of cases with negative reflex cytology and normal colposcopy, with CIN2+ detected in 5.0% among positive HPV16/18 and 3.8% with non-16/18 HPV. Positive predictive value of high-grade colposcopic impression at FCV averaged 66.4% (range: 54.9-81.6% among our colposcopists) and is poorly correlated with early detection rate of CIN2+. Overall accuracy of colposcopy is 84.5% (range: 78.7-90.3%), buoyed by high true negative colposcopic predictions secondary to high rates of negative reflex cytology referral with the new screening algorithm and is also unlikely to be a useful colposcopy indicator., Conclusions: Early detection rate of CIN2+ within the first six months of presentation is a useful measure of colposcopy competency and we would encourage our National Cancer Screening Register to explore this with the participating colposcopists., (© 2024 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objectives: Histopathological diagnosis of colposcopically identified cervical lesions is a critical step for the recognition of cervical cancer precursors requiring treatment. Although there have been efforts to standardize the histologic diagnosis of cervical biopsy specimens, in terms of terminology and use of biomarkers, there is no uniform approach in the pathology community. Adjunctive p16 immunohistochemistry (IHC) can highlight precancer diagnoses, with use recommendations outlined by the Lower Anogenital Squamous Terminology project., Methods: We assessed the diagnostic reproducibility of cervical histopathological biopsy specimens with and without p16 staining among 2 expert pathologists., Results: Interpretation of p16 IHC as positive vs negative was highly reproducible (92.5% agreement, κ = 0.85); greater variation was seen in the choice of which biopsy specimens required adjunctive p16 staining (78.0% agreement, κ = 0.43). Adjunctive p16 IHC did not significantly increase diagnostic agreement under multitiered grading systems (benign vs cervical intraepithelial neoplasia [CIN] 1/low-grade squamous intraepithelial lesion vs atypical squamous metaplasia vs CIN2/high-grade squamous intraepithelial lesion [HSIL] vs CIN3/HSIL-CIN3 vs cancer) (65.5% agreement, κ = 0.56 without p16; 70.0% agreement, κ = 0.58 with p16). However, when dichotomizing diagnoses based on clinical management (less than HSIL vs HSIL+), diagnostic agreement increased with p16 IHC (90.5% agreement, κ = 0.79 without p16; 92.0% agreement, κ = 0.84 with p16). For biopsy specimens taken from women positive for human papillomavirus (HPV) type 16, agreement was similar with or without adjunctive p16 (κ = 0.80 without p16; κ = 0.78-0.80 with p16). In contrast, p16 IHC substantially improved diagnostic agreement for cervical biopsy specimens taken from women positive for other high-risk HPV strains, producing improvements in κ from 0.03 to 0.24., Conclusions: Adjunctive p16 immunostaining provides useful information in the evaluation of cervical biopsies for precancer. In our study, we have demonstrated that it is highly reproducible between 2 pathologists, although the decision of which biopsies warrant its use is less so. Furthermore, although p16 IHC showed a limited increase in diagnostic reproducibility for all biopsies included in our study, it did demonstrate a more sizable gain in biopsies negative for HPV 16 but positive for other high-risk genotypes. Further studies are needed to clarify the role of p16 IHC and how it can be optimized for the detection of cervical precancer, particularly in HPV-vaccinated populations where types other than HPV 16 are relatively more important., (© American Society for Clinical Pathology, 2024.)

Objective: To describe the prevalence of cervical intraepithelial neoplasia (CIN), high-risk human papillomavirus (hrHPV) infection, and cervical cancer in a high-risk, underscreened incarcerated population and to evaluate the performance of current cervical cancer screening options to detect cervical precancer (CIN 2/3) in this population. Study Design: Deidentified data were obtained from all cytological, hrHPV DNA, and histopathological testing of cervical biopsies performed on people incarcerated at the North Carolina Correctional Institute for Women between January 1, 2013, and December 31, 2020. These were linked to corresponding demographic data. The proportions of histopathological diagnoses of CIN2+ and CIN3+ immediately preceded by abnormal cytology testing or hrHPV testing were determined, and prevalence differences and 95% confidence intervals were calculated. Results: A total of 15,319 individuals incarcerated at the North Carolina Correctional Institute for Women had at least one cytology result during 2013-2020. Of these, 2,829 (18%) had abnormal cervical cytology, and 3,724 (24.3%) had positive hrHPV testing. The detection of CIN2+ was 95.9% by preceding abnormal cervical cytology, 89.9% by preceding positive hrHPV testing ( p = 0.03), and 96.5% by preceding positive co-testing. The detection rate of CIN3+ was 96.6% by preceding abnormal cervical cytology, 90.8% by preceding positive hrHPV testing ( p = 0.12), and 96.6% by positive co-testing. Conclusion: In our sample, primary cytology and co-testing detected CIN2+ at higher rates when compared with primary hrHPV testing. This reinforces that incarcerated populations do not fall into average-risk populations for which current cervical cancer screening options are designed, which should be considered when performing screening in this population.

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., (© 2024. The Author(s).)

Study Question: Is cervical intraepithelial neoplasia (CIN) associated with reduced fecundability, defined as the probability of conceiving per menstrual cycle?, Summary Answer: Overall, we observed no meaningful association between CIN and fecundability, regardless of surgical status, although a recent diagnosis of moderate or severe CIN might be associated with slightly reduced fecundability for 2 years after diagnosis., What Is Known Already: About 15% of couples experience infertility. Few studies have examined the influence of CIN on fertility, and the results have been inconsistent. No study has investigated the association between fecundability and pathologist-reported CIN diagnoses, particularly with respect to the recency of the specific CIN diagnoses., Study Design, Size, Duration: This prospective cohort study included 9586 women trying to conceive. The women were enrolled from 1 June 2007 to 3 February 2020., Participants/materials, Setting, Methods: Women were invited to complete a baseline questionnaire and bimonthly follow-up questionnaires for up to 12 months or until pregnancy occurred. Data on cervical cytologies and biopsies were retrieved from The National Pathology Registry (DNPR), which holds records of all cervical specimens examined in Denmark. Women were categorized based on their most severe diagnosis of CIN: no lesion, other cervical changes, mild CIN (CIN1), or moderate/severe CIN (CIN2+) with or without surgery. To investigate the association between CIN and fecundability, we computed fecundability ratios (FR) and 95% confidence intervals (CI) using a proportional probabilities regression model. We adjusted for age at study entry, partner age, body mass index, smoking status, timing of intercourse, parity, education, number of sexual partners, and household income., Main Results and the Role of Chance: Compared with no lesion, the adjusted FRs (95% CI) for the association between CIN and fecundability were: other cervical lesions, 0.97 (0.91-1.04); CIN1, 1.04 (0.96-1.13); CIN2+ no surgery, 1.00 (0.82-1.22); and CIN2+ with surgery 0.99 (0.89-1.10). The FRs (95% CI) for a recent diagnosis (<2 years) of CIN were 0.98 (0.86-1.11) for other cervical lesions; 1.13 (0.99-1.29) for CIN1; 0.89 (0.62-1.26) for CIN2+ no surgery and 0.91 (0.75-1.10) for CIN2+ with surgery compared with the no lesion group., Limitations, Reasons for Caution: In the analyses, we adjusted for several covariates related to the women. However, we had little information on the male partners which could lead to unmeasured confounding as fecundability is a couple-based measure of fertility. Furthermore, a CIN diagnosis may not be constant as it may regress or progress spontaneously; therefore, it is possible that we have misclassified some women, especially women categorized as having normal cells or CIN1., Wider Implications of the Findings: Our results contribute important knowledge to women who are concerned about their future fertility after receiving a CIN diagnosis., Study Funding/competing Interest(s): This study was funded by The Danish Cancer Society (R167-A11036-17-S2). The overall cohorts were funded by the National Institute of Child Health and Human Development (R01-HD086742 and R03-HD094117). The authors report no competing interests., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The present study was aimed at showing the importance of HPV DNA status and the clinical history of the patients required by the cytologist for accurate reporting. A total of 1250 symptomatic women who attended the gynaecology outpatient department of the Mahavir Cancer Sansthan and Nalanda Medical College, Patna, for pap smear examinations were screened and recruited for the study. Due to highly clinical symptoms out of the negative with inflammatory smears reported, one hundred and ten patients were randomly advised for biopsy and HPV 16/18 DNA analysis by a gynaecologist to correlate negative smears included in the study. Pap smear reports revealed that 1178 (94.24%) were negative for intraepithelial lesions (NILM) with inflammatory smears, 23 (1.84%) smears showed low-grade squamous intraepithelial lesions (LSIL), 12 (0.96%) smears showed high-grade squamous intraepithelial lesions, and 37 (2.96%) smears showed an atypical squamous cell of undetermined significance (ASC-US). A biopsy of 110 out of 1178 (NILM) patients revealed that 15 (13.63%) women had cervical cancer, 29 women had CIN I, 17 women had CIN II + CIN III, 35 women had benign cervical changes, and 14 women had haemorrhages. On the other hand, HPV 16/18 DNA was detected as positive in 87 out of 110. The high positivity of HPV in biopsied cases where frank cervical cancer and at-risk cancer were also observed in the negative smear-screened patients reveals that the HPV status and clinical history of the patients will be quite helpful to the cytologist for accurate reporting, and suggests that a negative HPV DNA result may be a stronger predictor of cervical cancer risk than a negative Pap test., (© 2024. The Author(s).)

Background: Cervical cancer screening results that are negative for cytology but positive for high-risk human papillomavirus (HR-HPV) are not uncommon. One-year follow-up is suggested for patients with no history of HPV positivity under the most recent American Society of Colposcopy and Cervical Pathology (ASCCP) guidelines (2019). The aim of this study was to evaluate the immediate risk of cervical intraepithelial neoplasia (CIN) among cytology-negative patients positive for HR-HPV. The diagnostic accuracy of colposcopy in these patients was investigated., Methods: A retrospective study was conducted in patients who were cytology negative but HR-HPV positive and referred for colposcopy from January 2022 to August 2023. Patients were compared in terms of the immediate rate of CIN lesions among the HPV16-positive group, the HPV18-positive group and the non-16/18 HR-HPV-positive group. The distribution of CIN2 + lesions according to age was evaluated. The factors associated with the accuracy of colposcopy were evaluated using univariate and multivariate logistic regression., Results: Among the 372 patients, 195 had chronic cervicitis, 131 had CIN1, 37 had CIN2/3, and nine had carcinoma. The immediate rates of CIN2 + lesions and CIN3 + lesions in patients who were not HR-HPV16/18-positive were comparable to those in patients who were HPV16/18-positive (P = 0.699). In addition, among patients diagnosed with CIN2 + lesions, 8 (17.39%) patients were women aged < 30 years. When pathological results were used as a reference, the consistency rate of colposcopy was 61.0% (227/372). Multivariate analyses revealed that age and the type of cervical transformation zone were independent factors affecting the accuracy of colposcopy (P < 0.001)., Conclusions: In countries with limited resources, immediate colposcopy referral should be recommended for patients who are cytology negative but HR-HPV-positive (including non-16/18 HR-HPV-positive), and cervical cancer screening via cotesting should be suggested for women aged < 30 years. Colposcopy has moderate diagnostic value and can be affected by age and the type of cervical transformation zone., (© 2024. The Author(s).)

Aim: There is currently no protocol for classifying patients with HPV persistence and preoperative stenosis of the cervical canal. This has a significant impact on cytology results, colposcopy results and the possibility of obtaining reliable cervical histology outcomes. Our analysis clearly shows that colposcopy and cytology underestimate the histological results in patients with limited visibility due to the presence of a type 3 transformation zone (TZ). Our analysis revealed a significant discrepancy between the colposcopy and cytology results and the histological outcomes. Insufficient colposcopy led to the underdiagnosis of dysplastic lesions in patients with a type 3 TZ and cervical stenosis. In the case of repeated cytological abnormalities and inadequate colposcopy examination, it is crucial to perform a diagnostic conization to exclude high-grade dysplastic changes and cervical carcinoma., Methods: We conducted a retrospective analysis of 1,021 conizations performed in tertiary care hospital in Wolfsburg, Germany between 2014 and 2020. Of these surgical procedures, 89 were diagnostic conizations. In our analysis, we defined diagnostic conization as a procedure performed when there is HPV persistence and repeated cytologic abnormalities in combination with a type 3 TZ, and when it is not possible to retrieve a relevant cervical histology sample., Results: In this period, 8.7% of all conizations were diagnostic excisions. We found histological abnormalities in 48 of 89 patients (53.9%). The histological examination of the excised cone revealed high-grade cervical intraepithelial neoplasia (CIN/HSIL) in 9 patients (10.1%) and CIN 2+ (HSIL) in 23 out of the 89 patients (25.8%). Two cases of early-stage cervical carcinoma (FIGO IA1 and FIGO IA2) were confirmed (2.3%)., Conclusion: Patients with cervical stenosis, high-risk HPV persistence and repeated cytological abnormalities are at high risk of undetected high-grade cervical dysplasia. Histologic confirmation must be ensured in this patient consultation and this can be achieved by performing diagnostic excisions., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Background: Immunohistochemistry (IHC) is widely used in the management of patients with cervical intraepithelial neoplasia (CIN) but still has many limitations in clinical practice. We analyzed the correlation of new biomarkers with the severity of CIN and follow-up outcomes in patients after conization to improve the management of patients with CIN., Methods: IHC staining of Eag1 and p16/Ki-67 was performed on cervical tissue sections from 234 patients with suspected CIN2/3. After a series of follow-ups, including human papillomavirus (HPV) test and thinprep cytologic test (TCT) for 1-2 years, the outcomes were collected. IHC scores of biomarkers and follow-up results were used to analyze the correlation and assess the diagnostic efficiency of biomarkers., Results: The IHC staining intensity of Eag1 and p16/Ki-67 was significantly different from that of the CIN1-3 groups (p < 0.05). Eag1 expression scores were significantly different in the distribution between the two follow-up groups (p < 0.001). ROC curves based on the correlations between the follow-up outcomes and the Eag1 scores and IS of p16/ki-67 showed that Eag1 had a greater AUC (0.767 vs. 0.666). Logistic regression analysis of the combination of biomarkers revealed a greater AUC value than any single biomarker., Conclusions: Eag1 expression was significantly correlated with CIN grade and follow-up outcomes after conization. IHC staining of combinations of biomarkers of Eag1, p16 and Ki-67 may help us to improve the ability to identify risk groups with abnormal follow-up outcomes after treatment for CIN., (© 2024. The Author(s).)

Objective: This study aimed to evaluate whether severity changes with colposcopic lesion size, regardless of age., Methods: This retrospective comparative study reviewed the records of 428 women with altered cytopathology reports who were directed by primary health care. Only those women with colposcopic alterations were evaluated (n=411). Histopathological analyses were restricted to patients who underwent excisional treatment (n=345). According to their age, they were grouped into the following: <21, 21-24, 25-35, and >35 years, and also, ≤24 and ≥25 years. The cytopathological, colposcopic, and histopathological findings were grouped according to severity. Lesion size was subjectively assessed from the colposcopic drawing recorded in the chart and according to the number of quadrants of the total cervical surface affected by colposcopic alterations in the transformation zone. Statistical significance was set at p<0.05., Results: The evaluations suggested that the lesion size was directly related to the severity of the cytopathology, colposcopy, and histopathology reports for the age groups ≤24 or ≥25 years. We observed associations between lesion size and severity of the cytopathology (≤24 years, p=0.037) and histopathology (≥25 years, p=0.003) findings., Conclusion: The size of the lesion was directly related to the severity of the histopathological lesion in patients aged ≥25 years and cytopathological in patients aged ≤24 years.