Cervical Intraepithelial Neoplasia Research Articles

The impact of Germany’s human papillomavirus immunization program on HPV-related anogenital diseases: a retrospective analysis of claims data from statutory health insurances

PurposeHuman papillomavirus (HPV) is the most common sexually transmitted infection, responsible for multiple HPV-related diseases, including almost all cervical cancers. The highly effective HPV vaccination has been recommended under the German HPV national immunization program (NIP) since 2007 and is reimbursed by health insurances. Vaccination uptake rates, however, remain suboptimal and data on the real-world impact of HPV vaccination in Germany are lacking. This study aims to demonstrate the population-level impact of Germany’s NIP on HPV-related anogenital diseases among young women.MethodsRetrospective claims data analysis using a classic impact study design comparing disease prevalence among 28- to 33-year-old women before and after introduction of the HPV-immunization program in Germany. Claims data representing approximately two thirds of German health insurances were used. HPV-related disease outcomes included cervical cancer and high grade precancers (cervical intraepithelial neoplasia (CIN) 2+), anogenital warts, as well as vulvar, vaginal, and anal precancer/cancer.ResultsSignificant declines were seen for CIN2+, anogenital warts, and vaginal precancer/cancer. Prevalence of CIN2+ declined 51.1% from 0.92% (95% CI = 0.78%, 1.08%) to 0.45% (95% CI = 0.38%, 0.53%). There was a 38.6% decline in anogenital warts prevalence from 0.44% (95% CI = 0.36%, 0.54%) to 0.27% (95% CI = 0.22%, 0.32%) and 75.0% decline in vaginal precancer/cancer prevalence from 0.04% (95% CI = 0.02%, 0.07%) to 0.01% (95% CI = 0.00%, 0.02%).ConclusionThe German HPV-immunization program has led to significant declines in female anogenital disease among young women in Germany, highlighting the importance of the vaccination. Moreover, the data suggest that increasing vaccination coverage in Germany could further strengthen the public-health impact of its HPV-immunization program.

Study on serum miR-182 as a marker for diagnosis and prognosis of cervical cancer.

Cervical cancer (CC) is a common female malignancy, with a global incidence rate second only to breast cancer. To propose a new idea for early treatment and auxiliary diagnosis of CC by exploring the diagnostic and prognostic implications of serum miR-182 in CC. We enrolled 70 CC patients, 35 cervical intraepithelial neoplasia (CIN) patients and 35 healthy controls (HCs), who visited The First Affiliated Hospital of Hainan Medical College Hospital between January 2015 and April 2016. miR-182 expression was quantified by real-time quantitative PCR and compared among the three groups. The correlation of serum miR-182 expression with patients' clinical features was evaluated. The receiver operating characteristic curve (ROC) and the Kaplan-Meier method were used to evaluate the early diagnostic value and prognostic value of serum miR-182. Cox regression analysis was performed to determine serum miR-182 expression and its important role in predicting CC patients' prognosis. Serum miR-182 expression was determined to be 0.345 ± 0.094, 0.369 ± 0.076, and 0.586 ± 0.157 in CC patients, CIN patients, and HCs, respectively (P< 0.001). Serum miR-182 expression had an obvious association with lymph node metastasis and pathological differentiation (P< 0.05). The area under the ROC curve (AUC) of serum miR-182 was 0.709 (95% CI: 0.622-0.795), the critical value was 0.456, the sensitivity was 81.4%, and the specificity was 52.9%. CC patients were grouped as either the low- (miR-182 < 0.3) or high-level group (miR-182 ⩾ 0.03) based on serum miR-182 levels, and a Cox regression model of OS was established. Serum miR-182 expression was identified as a factor independently influencing CC patients' OS (P= 0.028); the death risk of the high-level group was 3.246 times that of the low-level group. Serum miR-182 expression is not only a biomarker for early diagnosis of CC, but also one of the independent factors influencing the survival and prognosis of CC patients.

Polymorphisms in miRNA Genes Targeting the AMPK Signaling Pathway are Associated with Cervical Cancer Susceptibility in a Han Chinese Population.

Cervical cancer (CC) poses a significant threat to women's health worldwide, and multiple signaling pathways have been confirmed to be involved in its development. The AMPK signaling pathway plays a central role in maintaining energy homeostasis, and its dysregulation is closely associated with the occurrence of CC. Changes in microRNA (miRNA) expression levels might be related to the AMPK signaling pathway. Single nucleotide polymorphisms (SNPs) can affect the function of miRNA and result in the development of CC. To investigate the association between the SNPs of AMPK pathway-associated miRNAs and CC in a Han Chinese population, we selected eight miRNA genes located in the AMPK pathway and analyzed nine SNP loci within these genes to explore whether they are associated with genetic susceptibility to cervical intraepithelial neoplasia (CIN) and CC. A total of 2,220 subjects were included in this study, including 928 healthy controls, 421 CIN patients, and 871 CC patients. Nine candidate SNPs (rs895819 in miR-27a, rs10061133 in miR-449b, rs41291179 in miR-216a, rs76481776 in miR-182, rs10406069 in miR-5196, rs12803915 and rs550894 in miR-612, rs66683138 in miR-3622b, and rs2620381 in miR-627) were genotyped using the TaqMan method. The results showed significant differences in the allele distribution of rs41291179 and rs12803915 between the control group and the CIN group, as well as between the control group and the CC group (all P values < 0.005). The A allele of rs41291179 and the G allele of rs12803915 were associated with decreased risk of CIN (OR = 0.05, 95% CI: 0.01-0.39; OR = 0.61, 95% CI: 0.49-0.76) and CC (OR = 0.08, 95% CI: 0.01-0.66; OR = 0.71, 95% CI: 0.59-0.86), respectively. Our results suggest that polymorphisms in miRNA genes of the AMPK signaling pathway are associated with the development of CC.

1669P The burden of shame and guilt: Quality of life in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer – A preliminary study

1669P The burden of shame and guilt: Quality of life in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer – A preliminary study

To compare liquid based cytology and HPV DNA testing in detection of cervical intraepithelial Neoplasia

To compare liquid based cytology and HPV DNA testing in detection of cervical intraepithelial Neoplasia

Multiscale Optical Imaging Fusion for Cervical Precancer Diagnosis: Integrating Widefield Colposcopy and High-Resolution Endomicroscopy.

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. 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. 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). Our findings show that multiscale optical imaging of the cervix allows the highly sensitive and specific detection of high-grade precancers. The multiscale imaging system and MSFN could facilitate the accurate, real-time diagnosis of cervical precancers in low-resource settings.

Time trends in the clinical management of cervical intraepithelial neoplasia grade 2: A Danish register-based study.

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. 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). 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). 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.

Anesthesia Usage and Pain Management in Colposcopy: A Scoping Review of Efficacy and Approaches.

Colposcopies are diagnostic procedures conducted to detect precancerous and cancerous lesions on the cervixand are often done as a sequelae of histological abnormalities found on cervical screening exams, such as precancerous abnormalities, positive human papillomavirus (HPV) results, or a past medical history of cervical dysplasia. Colposcopies, while often necessary to ensure the health of the patient, can induce a lot of anxiety and distress in the time leading up to the procedure, often due to fear of the procedure itself, anticipation of pain, as well as fear regarding the results of the colposcopy. Experiencing physical pain and discomfort during gynecological procedures can negatively influence a woman's willingness to comply with future medical appointments, often exacerbating feelings of anxiety and distress. A systematic search was conducted to identify the relevant articles published within the last 10 years pertaining to pain management in colposcopy procedures. The search strategy aimed to identify studies involving the utilization of anesthesia or analgesics for pain management or prevention during colposcopy, with a focus on randomized controlled trials. This systematic review aims to review the existing literature on the use of anesthetics in colposcopy and its effect on patient outcomes, investigating the current strategies of anesthesia use in the setting of a colposcopy, as well as their efficacy in improving pain.

Changes in the molecular nodes of the Notch and NRF2 pathways in cervical cancer tissues from the precursor stages to invasive carcinoma.

Cancer is a multifactorial disease characterized by the loss of control in the expression of genes known as cancer driver genes. Cancer driver genes trigger uncontrolled cell replication, which leads to the development of malignant tumors. A cluster of signal transduction pathways that contain cancer driver genes involved in cellular processes, such as cell proliferation, differentiation, apoptosis and dysregulated organ growth, are associated with cancer initiation and progression. In the present study, three signal transduction pathways involved in cervical cancer (CC) development were analyzed: The Hippo pathway (FAT atypical cadherin, yes-associated protein 1, SMAD4 and TEA domain family member 2), the Notch pathway [cellular-MYC, cAMP response element-binding binding protein (CREBBP), E1A-associated cellular p300 transcriptional co-activator protein and F-Box and WD repeat domain containing 7] and the nuclear factor erythroid 2-related factor 2 (NRF2) pathway [NRF2, kelch-like ECH-associated protein 1 (KEAP1), AKT and PIK3-catalytic subunit α]. Tumor samples from patients diagnosed with various stages of CC, including cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3, in situ CC and invasive CC, were analyzed. The mRNA expression levels were analyzed using reverse transcription-quantitative PCR assays, whereas protein expression levels were assessed through immunohistochemical tissue microarrays. High mRNA expression levels of c-MYC and AKT and low expression levels of NRF2 and KEAP1 were associated with a decreased survival time of patients with CC. Additionally, increased expression levels of c-MYC were detected in the invasive CC stage. At the protein level, increased NRF2 expression levels were observed in all five stages of CC samples compared with those in the cancer-free control samples. AKT1 was found to be dysregulated in the CIN 1 and CIN 2 stages, PI3K in the in situ and invasive stages, and CREBBP in the CIN 3 and in situ stages. In summary, the present study demonstrated significant changes in proteins of the Notch and NRF2 pathways in CC. NRF2 was overexpressed in all cervical cancer stages (cervical intraepithelial neoplasia, in situ CC and invasive CC). The present study makes an important contribution to the possible biomarker proteins to be analyzed for the presence of premalignant and malignant lesions in the cervix.

The Value of Human Epididymal Protein 4, Carcinoembryonic Antigen and Alpha-Fetoprotein in the Early Diagnosis of Cervical Cancer

Objectives: This research aimed to unveil the value of human epididymal protein 4 (HE4), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in the early diagnosis of cervical cancer. Design: This was a clinical study. Participants: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with cervical intraepithelial neoplasia (CIN) (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. Setting: The review was conducted in a Jiaxing First Hospital. Methods: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with CIN (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. The expression levels of serum HE4, CEA, and AFP in the three groups were detected, and the correlation between the levels of serum HE4, CEA, and AFP and the clinicopathological characteristics of patients with early stage cervical cancer were analyzed, and the receiver operating characteristic (ROC) curves were plotted to identify the value of the single and triple tests of serum HE4, CEA, and AFP for the early stage diagnosis of cervical cancer. Results: The levels of serum HE4, CEA, and AFP in the early stage cervical cancer group were higher than those in the disease control and the healthy control groups (p < 0.05). The levels of serum HE4, CEA, and AFP were related to the FIGO stage as well as the histological grading of patients with early stage cervical cancer (p < 0.05). The results of the ROC curves revealed that the AUC areas of HE4, CEA, and AFP for single as well as triple diagnosis of patients with early stage cervical cancer were 0.725, 0.679, 0.663, and 0.811, respectively, and the AUC of the three combined tests was markedly higher than that of HE4, CEA, AFP single test (p < 0.05). Limitations: There is a lack of larger sample sizes to test whether the combined HE4, CEA, and AFP detection has sufficient validity at the individual level and there are not enough serum samples in this study to perform circulating HPV-DNA detection and compare it with the levels of serum markers. Conclusion: The combination of HE4, CEA, and AFP has good clinical reference value analysis in the auxiliary diagnosis of early stage cervical cancer, and it is worthy of further validation and popularization.

Cold Knife Conization Vs. Loop Electrosurgical Excision Procedure in Premalignant Cervical Lesions in a Cohort of Females in Romania

Cold knife conization and loop electrosurgical excision procedures (LEEP) are two methods of minimally invasive treatment used in Romania for high-grade cervical dysplasia. The purpose of this study is to identify correlations between the results of the Papanicolaou (PAP) smear and biopsy and to evaluate the positivity of resection margins in both types of conizations: cold knife conization versus LEEP. The 96 cases enrolled in this study were gathered from ‘Prof. Dr. Ioan Pușcaș’ City Hospital of Șimleu Silvaniei, Romania, in a time interval from 01.01.2022 to 01.01.2024. The results of our study showed that out of 20 women who underwent PAP smear for ASC-US, 4 were actually found to have high-grade squamous intraepithelial lesion (H-SIL) according to biopsy results. The estimated risk in females who underwent LEEP procedure with positive margins in the histopathological examination, in the studied population, is almost 0.5 times higher compared to those who underwent cold knife conization. Histopathological examination of cervical specimens is the gold standard method in detecting high-risk cervical lesions. Our study shows that positive deep endocervical margins are more likely to occur in loop electrosurgical excision procedures compared with cold knife conization.

Safety profile of levonorgestrel intrauterine system: Analysis of spontaneous reports submitted to FAERS

The levonorgestrel-releasing intrauterine system (LNG-IUS) is an established, long-acting contraceptive option. With the widespread use of the LNG-IUS, drug-reported adverse events (AEs) have also garnered significant attention. In this study, we conducted a real-world analysis using the FDA's Adverse Event Reporting System (FAERS) database to assess the incidence of AEs associated with LNG-IUS use. Data from FAERS spanning from 2004Q1 to 2024Q1 were reviewed, with a focus on reports in which LNG-IUS was the primary suspected and secondary suspect drug. Signal detection was carried out utilizing Standardized MedDRA Queries (SMQ) and Preferred Terms (PT), with reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) employed to identify Signals of Disproportionate Reporting (SDR) for AEs. A positive SDR was defined when all three methods indicated significance. Analysis of 13 SMQs revealed notable SDRs in ear and eye disorders, cardiac arrhythmias, and lipodystrophy. Of the 61 suspected SDRs identified at the PT level, nearly half were not previously documented in labeling. Key potential signals of AEs associated with LNG-IUS use included increased heart rate, papilledema, idiopathic intracranial hypertension, cervical dysplasia, ruptured ovarian cyst, and uterine embedment and perforation. The findings underscore the importance of signal detection using FAERS data for identifying safety concerns related to LNG-IUS. Long-term observational studies are warranted to confirm and further elucidate these potential safety signals.

Vaccination in latent papillomavirus infections: An experimental randomized, prospective, open-label, controlled trial

Background. Human papillomavirus refers to one of the most common sexually transmitted infections with the majority of viruses in the host being transient carriers, the so-called latent forms of papillomavirus infection. Persistence of cancer-associated human papillomavirus is fraught with cervical intraepithelial neoplasia, and subsequent cervical cancer. Measures for secondary prevention of cervical cancer in latent forms of papillomavirus infection are yet to be developed, which predetermined the present study.Objectives. To increase the effectiveness of secondary prevention of cervical cancer by improving the algorithm for managing latent forms of papillomavirus infection in women. Methods. A randomized controlled trial enrolled 152 patients diagnosed with a latent papillomavirus infection. Patient examination and data analysis were carried out at clinical trial centers of the Department of Obstetrics, Gynecology and Perinatology of Kuban State Medical University (Russia) in 2020–2024. The trial involved patients aged 18 to 35 years. Patients were divided into 2 groups using the sealed code envelope method: Group I (comparison group) (n = 74) — microbiological sanitation of the cervicovaginal zone (as indicated) and observation for 36 months with annual control of viral load, colposcopy and oncocytology; Group II (study group) (n = 78) — microbiological sanitation of the cervicovaginal zone (as indicated) and administration of quadrivalent recombinant human papillomavirus vaccine (types 6, 11, 16, 18) (3 doses intramuscularly: second and third doses were administered 1 and 3 months after the first one). Each patient was analyzed for the effectiveness of preventive therapy according to the dynamics of indicators: colposcopy, cytology (Papanicolau staining), and molecular biological analysis (polymerase chain reaction). The indicators were evaluated after 12, 24, and 36 months. Statistical analysis of the results was carried out using IBM SPSS Statistics 26 (IBM, USA) variation statistics programs.Results. Vaccination with a quadrivalent recombinant vaccine against human papillomavirus of types 6, 11, 16, 18 against the background of correction of dysbiotic vaginal and cervical disorders in latent forms of papillomavirus infection in women was revealed to cause a 9.3-fold decrease (compared to the study group) in realization of latent persistence of viruses into subclinical (25.7 % in group I vs. 9.0 % in group II) and clinical forms of papillomavirus infection (cervical intraepithelial neoplasia) — 12.1 % in group I vs. 1.3 % in group II, to reduce the persistence of human papillomavirus and the appearance of their new genotypes, the viral load of highly oncogenic types of human papillomavirus (1.9 times —3.2 ± 2.4 geq/ml in group I versus 1.7 ± 2.1 geq/ml in group II).Conclusion. The trial has shown that human papillomavirus vaccination is associated with a reduced risk of realization of latent forms of papillomavirus infection into clinical forms as cervical intraepithelial neoplasia and, consequently, cervical cancer, thereby being considered promising for secondary prevention of this pathology.

Intravaginal artesunate pessaries for treatment of cervical intraepithelial neoplasia 2/3 among HIV-positive and HIV-negative women in Kenya: Study protocol for a pilot trial.

Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), which bear 90% of deaths. Current precancer treatments rely on healthcare workers who may be out of reach for many women. Development of a patient-controlled cervical precancer treatment can significantly improve access in remote areas and promote secondary prevention of cervical cancer. This is a phase I trial among 18 HIV-positive and HIV-negative women in Kenya, investigating use of artesunate vaginal pessaries as treatment for cervical precancer among women screening positive for cervical precancer who need excisional treatment. The primary objective will be the safety of self-administered artesunate pessaries. Participants will self-administer 200mg of artesunate vaginally daily for 5 days, followed by a drug-free week, repeated for a total of 4 cycles (artesunate self-administration on weeks 1, 3, 5, 7). The total study duration, including participant follow-up is 48 weeks. Safety and adherence will be assessed through review of symptom diaries and biweekly follow-ups during the treatment phase. Data analysis will include quantitative and qualitative methods. Figure 1 illustrates the study schema. Considering the challenges associated with excisional treatments for cervical precancer in LMICs where access to care is limited, this study proposes an alternative approach using intravaginal Artesunate. This clinical trial will provide important safety and efficacy data on using artesunate as a topical therapy for both HIV-positive and HIV-negative women. ClinicalTrials.gov identifier: NCT06165614.

The value of endocervical curettage during large loop excision of the transformation zone in combination with endocervical surgical margin in predicting persistent/recurrent dysplasia of the uterine cervix: a retrospective study

BackgroundCervical 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.MethodsIn 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).ResultsPatients 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.ConclusionOur 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.

Impact of Vaginal Microbiota on Cervical Intraepithelial Neoplasia, Human Papillomavirus Infection, and Cervical Cancer Prevention

Impact of Vaginal Microbiota on Cervical Intraepithelial Neoplasia, Human Papillomavirus Infection, and Cervical Cancer Prevention

AICyte-alone capabilities as an independent screener for triaging cervical cytology using a 50% negative cutoff value.

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. 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. 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. 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.

Surgical protocols for oral leukoplakia and precancerous lesions across three different anatomic sites.

This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.

Triage performance of PAX1m/JAM3m in opportunistic cervical cancer screening of non‒16/18 human papillomavirus-positive women: a multicenter prospective study in China

ObjectivesIn this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1m/JAM3m) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +).MethodsThe triage performance of liquid-based cytology (LBC) and the PAX1m/JAM3m test for detecting CIN3 + were compared.ResultsIn total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1m/JAM3m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1m/JAM3m( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837–0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1m/JAM3m(+). Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1m/JAM3m(+) were 3.3 (95% CI 2.0–5.9) and 42.6 (27.1–69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1m/JAM3m(+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8–100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7–26.8%).ConclusionsIn non-16/18 hrHPV(+) women, PAX1m/JAM3m was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity.

Cervical cancer screening efficacy using SurePath, ThinPrep and conventional cytology: A large data set analysis from the Japan Cancer Society.

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. 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. 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. 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.