Cervical Intraepithelial Neoplasia Lesions Research Articles

Distribution and Severity of Cervical Intraepithelial Neoplasia in Women With Different Human Papillomavirus: An Analysis From Liaoning Province of Northeastern China.

Persistent infection with high-risk human papillomavirus (HPV) is a key contributor to cervical intraepithelial neoplasia (CIN), but the relation between high-risk HPV genotypes and the location of CIN lesions remains unclear. The aims of this study were to investigate the most frequent biopsy site of CIN lesions in women with different HPV infection and to analyze the biopsy times, CIN frequency, and the clustering of CIN frequency based on 12-o'clock sites and cervical quadrant locations. We conducted a retrospective study of HPV detection and genotyping at the virology department of our hospital. Colposcopy exams were performed by specialists according to a standardized protocol, and all visually abnormal areas were further biopsied. Pearson chi-squared tests and cluster analyses were implemented to analyze the data. Among 1,381 women enrolled in this study, 933 cases infected with HPV. HPV16, HPV58, and HPV18 were the most common genotypes. The most frequent biopsy site was the 6 o'clock position. The highest frequency of high-grade CIN findings in single-genotype HPV groups was the 6 o'clock position and that for multiple-genotype HPV group was the 12 o'clock location. All CIN clusters were found in the 6 and 12 o'clock biopsy sites, except in the HPV18 group. Quadrant 2 and 4 were clustered in most groups. The 6 and 12 o'clock sites in cervical quadrant 2 and 4 should be targeted during cervical biopsy procedures. These findings can provide clinicians with specific recommendations on the optimal site for CIN biopsy when considering the HPV genotype.

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

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

PAX1 and SOX1 gene methylation as a detection and triage method for cervical intraepithelial neoplasia diagnosis.

Methylation assays have demonstrated potential as dependable and high-precision approaches for identifying or triaging individuals with cervical cancer (CA) or cervical intraepithelial neoplasia (CIN). Our investigation aimed to assess the efficacy of diagnosis and triage of the PAX1/SOX1 methylation panel in detecting CIN or CA. A total of 461 patients with abnormal high-risk human papillomavirus (hrHPV) or cytology test results were recruited for this study. Each patient underwent an assortment of assessments comprising cytology test, hrHPV test, colposcopy examination, and PAX1 and SOX1 methylation test. The extent of methylation of both genes demonstrates a positive correlation with the severity of CIN lesions and CA. To determine the correlation for patients with CIN2 or worse (CIN2+), the area under curve (AUC) was 0.821 (95%CI 0.782-0.853) for PAX1 and 0.800 (95%CI 0.766-0.838) for SOX1, while for CIN3 or worse (CIN3+),0.881 (95%CI 0.839-0.908) for PAX1 and 0.867 (95% 0.830-0.901) for SOX1. The PAX1/SOX1 methylation marker panel performed sensitivity and specificity of 77.16% and 91.67% for CIN2+, 84.76% and 90.50% for CIN3+, respectively. Regarding triaging hrHPV+ patients, the PAX1/SOX1 methylation test only referred 11.83% of the patients who are unnecessary for coloscopy examination, which is comparatively lower than cytology， thereby signifying a promising triage strategy for hr-HPV positive women. Furthermore, we observed that the positive PAX1/SOX1 methylation test result for untreated CIN1 or less patients would result in a higher likelihood of progression upon a 24-month follow-up visit. The present investigation demonstrates that the PAX1/SOX1 methylation marker panel exhibits a favorable diagnostic performance in CIN detection and holds the potential to be employed for individual CIN tests or hrHPV-positive triage.

Exploring the potential prompting role of cervical human papilloma virus detection in vulvar lesions: a cross-sectional study in China.

The etiology and clinical presentation of vulvar carcinomas, especially vulvar lesions, are not fully understood. Because the vulva and cervix are anatomically connected, human papillomavirus (HPV) is the main cause of cervical lesions. Thus, this study explored the potential characteristics and effects of specific HPV infection types across vulvar lesions and concurrent cervical lesions. This retrospective, cross-sectional study analyzed patients with cervical HPV or cytological results and concurrent vulvar biopsy who were seen in our hospital colposcopy clinic in Shanxi Province, China, between 2013 and 2023. Data on age, menopause status, vulvar manifestations, and cytology and HPV infection testing results were collected. Attributable fractions and multinominal logistic models were used to evaluate HPV genotyping and clinical characteristics across vulvar lesions. Among the 1,027 participants, 83 (8.1%) had vulvar intraepithelial neoplasia (VIN) of high grade or worse (VIN2+), and 127 (12.4%) had non-neoplastic epithelial disorders of the vulva (NNEDV). A total of 175 patients had either VIN2+ or cervical intraepithelial neoplasia (CIN) lesions of grade 2 or worse (CIN2+). The most common HPV genotypes for VIN2+ or concurrent VIN2+/CIN2+ were HPV16, HPV52, and HPV58, although attributable fractions differed among lesions. Patients with normal cytological or histopathological result were more likely to have NNEDV detected, while abnormal cervical diagnosis was associated with higher detection of VIN2+. Multinominal logistic modeling showed that age and HPV16 infection were risk factors for VIN2+ or concurrent VIN2+/CIN2+; however, only vulvar presentation with depigmentation was a risk factor for NNEDV. Among patients with low-grade CIN1/VIN1, compared with those who were HPV16 negative, those who were HPV16 positive were at 6.63-fold higher risk of VIN2+/CIN2+ [95% confidence interval (CI): 3.32, 13.21]. Vulvar depigmentation was also associated with increased risk of NNEDV (odds ratio: 9.98; 95% CI: 3.02, 33.04). Chinese women may be at specific, high risk for HPV infection types associated with VIN or CIN. The use of cervical cell HPV detection along with vulvar presentation during cervical cancer screening may also contribute to vulvar lesion detection.

The effects of the LaSota strain of oncolytic Newcastle disease virus vaccine on cervical intraepithelial neoplasia Patients-Clinical cohort study

BackgroundCervical cancer is one of the most common malignancies in women, and its treatment has many side effects. Therefore, in this research, the effects of the LaSota strain of oncolytic Newcastle disease virus vaccine on cervical intraepithelial neoplasia (CIN) patients were investigated. Methods15 patients who met the inclusion criteria and diagnosed as CIN II and CIN III were included in the study. The vaccine was injected inside the cervix (neoplasia site) at increasing doses during 21 days, and they were evaluated for adverse events. NDV antibody titer was measured in 90 days and the levels of ki-67 and p16 proteins were studied by immunohistochemistry. Also, the levels of some important inflammatory cytokines in the serum of CIN patients were measured and finally the patients were evaluated according to the final outcomes and the reduction of tumor lesions. ResultsOnly in the first dose of vaccine some patients showed flu-like symptoms. The accumulation of NDV antibodies started on the 7th day of the study and increased until the 90th day. Administration of LaSota vaccine had no significant effect on the expressions of Ki-67 and p16 proteins. Nevertheless, a decrease in the serum levels of Il-1β was observed in patients after the administration of the vaccine, but the serum levels of both Il-2 and INF-γ upregulated significantly. Also, vaccine administration had no significant effect in reducing CIN grades and lesions. ConclusionsIn general, we concluded that LaSota strain of NDV vaccine has no therapeutic effectiveness in CIN patients.

Relative Telomere Length in Cervical Exfoliated Cells among Women with High-Risk Human Papillomavirus

Introduction: This study investigates and compares the relative telomere length (RTL) outcome of high-risk (hr) human papillomavirus (HPV)-infected normal, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) cervical samples to HPV-free normal cervical samples. Methods: This study used archived cervical samples and obtained cytology and histology data. HPV genotyping was conducted using Sanger sequencing, and RTL was performed using real-time quantitative polymerase chain reaction. Results: This study investigated 287 cervical samples, including 100 normal and hr-HPV-negative samples from the control group, 44 normal and hr-HPV-infected samples, and 143 SIL and hr-HPV-infected samples. The RTL in hr-HPV-infected samples, including the SIL and normal sample groups, was significantly longer than that in the control group. RTL in HSIL (5.13 ± 3.22) and LSIL (2.86 ± 2.81) was significantly different (p < 0.001). The RTL of cervical intraepithelial neoplasia (CIN1) lesion (3.53 ± 2.53) differed significantly (p < 0.001) when compared to CIN2 and CIN3 lesions combined (12.04 ± 10.51). The risk of developing cervical cancer was associated with RTL and decreased with RTL. Conclusion: This study revealed the strong potential of the RTL test in identifying women at risk of developing cervical cancer.

Validation of an on-chip p16ink4a/Ki-67 dual immunostaining cervical cytology system using microfluidic device technology

More specific screening systems for cervical cancer may become necessary as the human papillomavirus (HPV) vaccine becomes more widespread. Although p16/Ki-67 dual-staining cytology has several advantages, it requires advanced diagnostic skills. Here, we developed an automated on-chip immunostaining method using a microfluidic device. An electroactive microwell array (EMA) microfluidic device with patterned thin-film electrodes at the bottom of each microwell was used for single-cell capture by dielectrophoresis. Immunostaining and dual staining for p16/Ki-67 were performed on diagnosed liquid cytology samples using the EMA device. The numbers of p16/Ki-67 dual-stained cells captured by the EMA device were determined and compared among the cervical intraepithelial neoplasia (CIN) lesion samples. Seven normal, fifteen CIN grade 3, and seven CIN grade 2 samples were examined. The percentage of dual-positive cells was 18.6% in the CIN grade 2 samples and 23.6% in the CIN grade 3 samples. The percentages of dual-positive staining increased significantly as the severity of the cervical lesions increased. p16/Ki67 dual immunostaining using the EMA device is as sensitive as the conventional method of confirming the histopathological diagnosis of cervical samples. This system enables a quantified parallel analysis at the individual cell level.

The relationship of immunohistochemical SOX-2 staining with histopathological diagnosis in patients with abnormal colposcopic findings.

This study aimed to analyze immunohistochemical staining and pathological data in cervical intraepithelial neoplasia (CIN) and squamous cell cervical carcinoma (SCC) with abnormal colposcopic findings. A histopathological evaluation of 45 low-grade squamous lesions (LSILs), 177 high-grade squamous lesions (HSILs) and 16 SCC biopsy materials from existing slides was obtained from blocks obtained from the archive. In addition, SOX-2 immunohistochemical staining was evaluated. The mean age of the HSIL group was 43.20 ± 8.97years, younger than the mean age of the LSIL group of 51.62 ± 9.64years (p = 0.000). There was no difference between the groups regarding the method of biopsy (p > 0.05). Endocervical gland involvement was not observed in the LSIL group, but was observed in 66 (37.3%) biopsy materials in the HSIL group (p = 0.000). There was a difference between the groups in terms of the level of CIN at the surgical margin (p = 0.000). Ki-67, SOX-2 staining percentage and p16INK4a positivity were higher in the HSIL group than in the LSIL group (respectively, 67.57 ± 19.10 vs. 14.62 ± 7.11, p = 0.000; 27.72 ± 31.56 vs. 10.09 ± 15.38, p = 0.003; 66 (82.5%) vs. 8 (44.4%), p = 0.001). While there was no difference in SOX-2 intensity between the HSIL and LSIL groups (p > 0.05), it was statistically significantly higher in the SCC group (p = 0.000), as was the percentage of SOX-2 (p = 0.000). We have shown that p16INK4a and SOX-2 staining is useful, in addition to Ki-67 immunostaining, which is widely used for SCC, which is one of the preventable cancer types. In addition, SOX-2 may provide a glimmer of hope in the development of SCC treatment modalities, especially since it is aggressively elevated in SCC rather than CIN lesions.

Development of an artificial intelligence-based diagnostic system for the detection of abnormal colposcopic findings.

82 Background: When performing colposcopic examinations in patients with abnormal cervical cytology, sufficient training is required to detect cervical intraepithelial neoplasia (CIN) with (1) high diagnostic accuracy and (2) minimizing time and reducing tissue biopsies. The aim of this study was to develop an artificial intelligence (AI)-based system that replicates expert colposcopic examination techniques to (1) identify CIN lesions with high accuracy and to (2) guide tissue sampling locations with high diagnostic performance, independent of examiner skill. Methods: A retrospective analysis was performed using 8341 colposcopic videos from 2013 to 2019, consisting of seven early-stage cervical cancer cases, 203 CIN3 cases, 276 CIN2 cases, and 456 CIN1 cases. An AI-based lesion detection model was constructed by annotating abnormal colposcopic findings after acetic acid processing in cervical cancer and CIN3 cases whose histologic diagnoses were confirmed by biopsies. The developed lesion detection model was applied to CIN1 and CIN2 cases, and the diagnostic accuracies of the lesions were evaluated. The accuracies of the lesions of CIN1 and CIN2 were evaluated according to the lesion area (sensitivity, specificity, area under the curve (AUC)) and the number of lesions identified. Results: The AI-based model was trained on 60 cases of cervical cancer and CIN3 and validated on 150 cases. The model was able to identify severe lesions with high accuracy, with a sensitivity of 85%, a specificity of 73%, an AUC of 0.89 for lesion area, and an accuracy of 95% for the number of lesions identified. The model also predicted abnormal colposcopic findings in CIN1 and CIN2 cases with high accuracy for detection of lesion area (sensitivity: 87% and 86%, specificity: 70% and 67%, AUC: 0.81 and 0.81, respectively) and identification of the number of lesions (97% and 93%, respectively). Furthermore, a heatmap display based on lesion prediction allowed visualization of the area with the highest acetic acid intensity corresponding to the actual biopsy locations. Conclusions: We have developed an AI-based diagnostic system for colposcopy that can identify CIN lesions with high accuracy and suggest appropriate biopsy sites. We are currently establishing an AI-based application for the visualization of abnormal lesions in colposcopy developed from the model, and anticipating its implementation in the clinical practice of colposcopic examinations.

The Fate of Cervical Dysplastic Lesions during Pregnancy and the Impact of the Delivery Mode: A Review.

Cervical dysplasia, also referred to as cervical intraepithelial neoplasia (CIN) or squamous intraepithelial lesion (SIL), is the precursor lesion of cervical carcinoma. Therefore, its diagnosis is vital for early detection and inhibiting the development of cervical carcinogenesis. Human papillomavirus (HPV) is the most common aetiology of cervical cancer and this infection mainly affects young women of childbearing age, thus affecting pregnant women as well. It is essential to know how CIN progresses in pregnant patients because the management of pregnant and non-pregnant patients is different (considering the safety of both mother and child in pregnancy). This review intends to highlight the studies which have assessed the rates of progression of CIN diagnosed in pregnancy throughout the antenatal period and the impact of the mode of delivery on CIN outcomes. We searched PubMed/MEDLINE and Google Scholar databases for relevant articles. Many studies indicate that the rate of progression of these lesions is very slow during the tenure of pregnancy; many also report postpartum regression of these lesions. Thus, in most of these patients, management can be safely implemented in the postpartum period while just keeping them under observation in the antenatal period. However, patients with high-grade CIN have a higher chance of developing invasive cancer and, therefore, require careful monitoring. There is a dispute regarding the role of the mode of delivery in determining the fate of cervical dysplasia. While some studies supported vaginal births over caesarean sections, others did not find any difference between the two in defining the outcome of the dysplastic lesions.

A pilot study of repeated 5-aminolevulinic acid photodynamic therapy for cervical intraepithelial neoplasia by a newly developed intravaginal irradiation system

The pilot study was performed to assess the usefulness of a newly developed patientand physician-friendly intravaginal irradiation system for photodynamic therapy with 5-aminolevulinic acid (5-ALA PDT) for cervical intraepithelial neoplasia (CIN). We used an intravaginal balloon applicator to make the cervix upright and to adjust the position and direction of the laser source in the vagina, resulting in minimal patient discomfort and minimal effort required by the physician during irradiation. Ten outpatients of CIN2 or 3 with high-risk human papillomavirus (HPV) infection without a history of HPV vaccination were treated by 5-ALA PDT. Each patient underwent PDT four times every two weeks. Nine patients showed pathological improvement, and the HPV clearance rate was 80%, and no recurrence was observed at two-years follow-up. Serum anti-HPV16 antibodies were detected in seven patients, and the antibody levels of three patients were high, equivalent to those acquired after HPV vaccination. Our newly developed irradiation system enabled easy repeat 5-ALA PDT in the outpatient clinic resulting in the improvement of CIN lesions and HPV clearance. Our results also suggested that repeated 5-ALA PDT might enhance HPV antibody production in CIN patients.

Pivotal Clinical Study to Evaluate the Efficacy and Safety of Assistive Artificial Intelligence-Based Software for Cervical Cancer Diagnosis.

Colposcopy is the gold standard diagnostic tool for identifying cervical lesions. However, the accuracy of colposcopies depends on the proficiency of the colposcopist. Machine learning algorithms using an artificial intelligence (AI) system can quickly process large amounts of data and have been successfully applied in several clinical situations. This study evaluated the feasibility of an AI system as an assistive tool for diagnosing high-grade cervical intraepithelial neoplasia lesions compared to the human interpretation of cervical images. This two-centered, crossover, double-blind, randomized controlled trial included 886 randomly selected images. Four colposcopists (two proficient and two inexperienced) independently evaluated cervical images, once with and the other time without the aid of the Cerviray AI® system (AIDOT, Seoul, Republic of Korea). The AI aid demonstrated improved areas under the curve on the localization receiver-operating characteristic curve compared with the colposcopy impressions of colposcopists (difference 0.12, 95% confidence interval, 0.10-0.14, p < 0.001). Sensitivity and specificity also improved when using the AI system (89.18% vs. 71.33%; p < 0.001, 96.68% vs. 92.16%; p < 0.001, respectively). Additionally, the classification accuracy rate improved with the aid of AI (86.40% vs. 75.45%; p < 0.001). Overall, the AI system could be used as an assistive diagnostic tool for both proficient and inexperienced colposcopists in cervical cancer screenings to estimate the impression and location of pathologic lesions. Further utilization of this system could help inexperienced colposcopists confirm where to perform a biopsy to diagnose high-grade lesions.

Distribution of cervical intraepithelial neoplasia is closely associated with HPV status and uterine position.

Although cervical intraepithelial neoplasia (CIN) lesions are considered to be not randomly distributed across the cervix, but predominantly in the anterior wall, the clinicopathological etiology remains unknown. Herein, we aimed to elucidate the relationship between quantitatively measured area of CIN2/3 and cervical cancer associated factors by retrospective cohort study. We analyzed 235 consecutive therapeutic conization specimens dissected as a single intact section to determine CIN2/3 area and its correlation with both clinical risk factors including human papillomavirus (HPV) status (single or multiple infection) and uterine position defined by transvaginal ultrasound. Cervical wall was classified into three groups: anterior: (11, 12, 1, and 2 o'clock), posterior (5, 6, 7, and 8 o'clock) and lateral (3, 4, 9, and 10 o'clock). Multiple regression revealed that younger age and HPV16 status were significantly correlated with CIN2/3 area (p = 0.0224 and p = 0.0075, respectively). The Jonckheere-Terpstra test showed a significant trend: CIN2/3 area was highest in the single HPV16 group, followed by the multiple HPV16 group and the non-HPV16 group (p < 0.0001). CIN2/3 area in the anterior wall was statistically significantly larger than the posterior and lateral wall (p = 0.0059 and p = 0.0107, respectively). CIN2/3 area in the anterior wall was significantly greater with anteversion-anteflexion than retroversion-retroflexion (p = 0.0485), whereas CIN2/3 area in the posterior wall was significantly larger with retroversion-retroflexion than anteversion-anteflexion (p = 0.0394). In conclusion, the topographical distribution of CIN2/3 area is closely associated with patient age, high-risk HPV status, especially single HPV16 infection and uterine position.

Androgen promotes squamous differentiation of atypical cells in cervical intraepithelial neoplasia via an ELF3-dependent pathway.

Since the human papillomavirus vaccines do not eliminate preexisting infections, nonsurgical alternative approaches to cervical intraepithelial neoplasia (CIN) have been required. We previously reported that FOXP4 (forkhead box transcription factor P4) promoted proliferation and inhibited squamous differentiation of CIN1-derived W12 cells. Since it was reported that FOXP expressions were regulated by the androgen/androgen receptor (AR) complex and AR was expressed on the CIN lesions, in this study we examined the effects of androgen on CIN progression. Since AR expression was negative in W12 cells and HaCaT cells, a human male skin-derived keratinocyte cell line, we transfected AR to these cell lines and investigated the effects of dihydrotestosterone (DHT) on their proliferation and squamous differentiation. We also examined the immunohistochemical expression of AR in CIN lesions. DHT reduced the intranuclear expression of FOXP4, attenuating cell proliferation and promoting squamous differentiation in AR-transfected W12 cells. Si-RNA treatments showed that DHT induced the expression of squamous differentiation-related genes in AR-transfected W12 cells via an ELF3-dependent pathway. DHT also reduced FOXP4 expression in AR-transfected HaCaT cells. An immunohistochemical study showed that AR was expressed in the basal to parabasal layers of the normal cervical epithelium. In CIN1 and 2 lesions, AR was detected in atypical squamous cells, whereas AR expression had almost disappeared in the CIN3 lesion and was not detected in SCC, suggesting that androgens do not act to promote squamous differentiation in the late stages of CIN. Androgen is a novel factor that regulates squamous differentiation in the early stage of CIN, providing a new strategy for nonsurgical and hormone-induced differentiation therapy against CIN1 and CIN2.

CIN grades possessing different HPV RNA location patterns and RNAscope is helpful tool for distinguishing squamous intraepithelial lesions in difficult cervical cases

Background and objectivesThe precise grading and characterization of cervical intraepithelial neoplasia (CIN) has been the focus of pathologists for a long time. This study aimed to explore known strategies for the grading of CINs.MethodsAfter routine H&E review, 85 lesions graded CIN 1, 2, or 3 were investigated primarily by HPV RNAscope to detect HR-HPV and LR-HPV, in combination with an HPV-DNA test and P16/Ki67 immunohistochemistry (IHC). Then, the 85 cases were divided into a control group (49 cases) and a test group (36 cases). The former consisted of cases with consistency between morphology, HPV DNA detection and P16/Ki67 IHC. We used them to evaluate HPV RNA distribution patterns in CINs of different grades. The latter were ambiguous cases in which pathologists could not confirm the diagnosis because of inconsistencies between morphology, HPV DNA detection and P16/Ki67 IHC. We reassessed them by comparison to the pattern in the control group.ResultsThe expression patterns of HPV mRNA signals were different in different CIN lesions. LSIL/CIN1 lesions were mostly expressed in superficial epithelium with diffuse clustered nuclear or cytoplasmic staining; HSIL/CIN2 were characterised by nuclear/cytoplasmic punctate or diffuse cluster nuclear staining in the mid-surface layer, and scattered nuclear/cytoplasmic punctate staining in basal and parabasal cells; whereas HSIL/CIN3 showed full-thickness nucleus/cytoplasmic scattered staining with a punctate pattern. According to the staining pattern, we corrected the diagnosis of 22 cases (22/36, 61.1%).ConclusionBecause of its distinct location pattern, HPV RNAscope has obvious advantages over the HPV-DNA test, and combined with P16/Ki67 IHC, it can help pathologists correctly grade CIN. In addition, it can effectively discriminate true CIN from normal or CIN mimic lesions, such as immature squamous metaplasia, atrophy, and inflammatory/reactive changes. Therefore, HPV RNAscope is a valuable auxiliary diagnostic test to avoid the overtreatment and undertreatment of CIN lesions.

Comparative Analysis between Reid’s Colposcopic Index and Swede’s Score for Detection of Premalignant Lesions of Cervix: A Prospective Study

Introduction: Colposcopy is an effective tool to detect premalignant lesions of the cervix. It is an observer-dependent technique; hence, various colposcopic-based scoring systems have been employed to minimise interobserver variations. Aim: To compare Reid’s Colposcopic Index (RCI) and Swede’s score for the detection of premalignant lesions of the cervix and compare it with colposcopic directed biopsy and histopathology. Materials and Methods: In this prospective observational study conducted at a tertiary care hospital in Delhi, India, between August 2019 to April 2020, 100 women of the reproductive age group were recruited. Pap (Papanicolaou) smear and colposcopy were done for all the patients. Scoring of colposcopic lesions was done according to Reid’s and Swede’s scoring system. In women with RCI or Swedes score ≥3, biopsy of the cervix for histopathology was carried out. Data was recorded and statistically analysed using Statistical Package for the Social Sciences (SPSS) software. Pearson and spearmen correlation coefficient was used for correlation of RCI and Swede’s score. Results: Mean age of women was 43.89±8.2 years. A positive correlation was found between RCI and Swedes score as the correlation coefficient was 0.995 and p-value&lt;0.001. Sensitivity was better with Swede’s scoring system as compared to RCI for predicting Cervical Intraepithelial Neoplasia (CIN)-I lesions. However, for predicting CIN-II and CIN-III lesions sensitivity with both the scoring system was comparable. The sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of RCI at a cut-off score of 5 was 54.54%, 87.17%, 54.54%, and 87.1% for CIN-I, for CIN-II was 100%, 86.67%, 45.45%, and 100%. CIN-III was 100%, 82.1%, 22.7%, and 100%. Similarly, the sensitivity, specificity, PPV, and NPV of Swedes score at a cut-off score of 5 was 59%, 84.6%, 52%, and 88% for CIN-I, for CIN-II was 100%, 83.33%, 40%, and 100%. And that for CIN-III was 100%, 78.94%, 20% and 100%. Conclusion: Both scoring systems performed well in predicting CIN lesions.

Can portable Colposcopes Replace Standard-of-care Colposcopes? A Crossover Trial of Two Portable Colposcopes with a Standard-of-Care Video Colposcope

Screen positive women need to be triaged by colposcopy which is a major challenge in low-middle income countries. Portable colposcopes may overcome many challenges, reduce referrals and enable a single visit approach. This study assessed the performance of portable colposcopes and potential to reduce referral. This crossover randomised study enrolled women aged 25 to 65 years with abnormal screening result or cervical symptoms. All women underwent visual inspection with acetic acid (VIA), HPV test, colposcopy with two portable colposcopes (Gynocular®, Gynius, Sweden, and Pocket® transvaginal colposcope, Duke University, NC, USA) and a standard video colposcope, and biopsy. Colposcopic Swede score agreement between portable and video colposcopes, as well as agreement of Swede score with histology were calculated for each device. The potential impact of portable colposcopes in a single visit approach was assessed based on the final diagnosis. Among 250 subjects, 27(10.80%) had high-grade cervical intraepithelial neoplasia (CIN2+) lesions. Swede scores for Pocket and Gynocular colposcopes were similar to video colposcope in 248 (99.20%) and 247 (98.80%) subjects, respectively (agreement scores 0.9969 and 0.9954, respectively). At a Swede score cut-off of ≥5, all three devices had identical sensitivity, specificity, positive and negative predictive value of 96.30%, 92.30%, 60.50% and 99.50,. Ablative treatment offered at field setting would result in optimal treatment in 52.0% and 85.1% cases when screened with VIA and HPV test respectively; using Pocket colposcope could improve this to 94.0% and 95.9%, respectively. Overtreatment and referral rates reduced from 46.8% and 12.4% to 4.8% and 6.0%, respectively, when VIA test is followed by triage with pocket colposcope. These outcomes were comparable to screening with HPV followed by colposcopy triage. Pocket colposcope performed comparably to the video colposcope. Used by healthcare providers in the field setting, they can augment the results of VIA significantly.

Distribution of microbiota in cervical preneoplasia of racially disparate populations

BackgroundsMicrobiome dysbiosis is an important contributing factor in tumor development and thus may be a risk predictor for human malignancies. In the United States, women with Hispanic/Latina (HIS) and African American (AA) background have a higher incidence of cervical cancer and poorer outcomes than Caucasian American (CA) women.MethodsHere, we assessed the distribution pattern of microbiota in cervical intraepithelial neoplasia (CIN) lesions obtained from HIS (n = 12), AA (n = 12), and CA (n = 12) women, who were screened for CC risk assessment. We employed a 16S rRNA gene sequencing approach adapted from the NIH-Human Microbiome Project to identify the microbial niche in all CIN lesions (n = 36).ResultsWe detected an appreciably decreased abundance of beneficial Lactobacillus in the CIN lesions of the AA and HIS women compared to the CA women. Differential abundance of potentially pathogenic Prevotella, Delftia, Gardnerella, and Fastidiosipila was also evident among the various racial groups. An increased abundance of Micrococcus was also evident in AA and HIS women compared to the CA women. The detection level of Rhizobium was higher among the AA ad CA women compared to the HIS women. In addition to the top 10 microbes, a unique niche of 27 microbes was identified exclusively in women with a histopathological diagnosis of CIN. Among these microbes, a group of 8 microbiota; Rubellimicrobium, Podobacter, Brevibacterium, Paracoccus, Atopobium, Brevundimonous, Comamonous, and Novospingobium was detected only in the CIN lesions obtained from AA and CA women.ConclusionsMicrobial dysbiosis in the cervical epithelium represented by an increased ratio of potentially pathogenic to beneficial microbes may be associated with increased CC risk disparities. Developing a race-specific reliable panel of microbial markers could be beneficial for CC risk assessment, disease prevention, and/or therapeutic guidance.

Evaluation of the Therapeutic Effect of Quadrivalent Human Papillomavirus (HPV) Vaccination on Cervical Intraepithelial Neoplasia Lesions.

Cervical cancer is the most common health problem among global young women. Cervical intraepithelial neoplasia (CIN) is a pre-invasive stage of cervical cancer, the major cause of which is human papillomavirus (HPV), and vaccination has a promising effect on reducing the progression of CIN lesions. The current study was a retrospective case control investigation in two centers, Shiraz and Sari Universities of Medical Sciences from 2018 to 2020 to evaluate the effect of quadrivalent HPV vaccination on CIN lesions (I, II, and III). Eligible patients diagnosed with CIN were selected and divided into two groups: one group received HPV vaccine and the control group did not. The patients were followed up after 12 and 24months. The information about tests (e.g., Pap smear, colposcopy, and pathology biopsy) and history of vaccination was recorded and statistically analyzed. 150 patients were classified into the control group (without HPV vaccination) and the other 150 patients were in the Gardasil group (with HPV vaccination). The patients' mean age was 32years old. Two groups were not significantly different according to age and CIN grades. Between two groups in 1 and 2years' follow-up examinations, the high-grade lesions in both Pap smear and pathology were significantly diminished in patients in the HPV vaccinated group in comparison with the control group with p-values 0.001 and 0.004 in 1year follow-up respectively and 0.00 after 2years follow-up. HPV vaccination can prevent the progression of CIN lesions in 2-year follow-up examination.

S891 Risk of Cervical Dysplasia/Cancer in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Introduction: There is inconsistent and conflicting evidence regarding the risk of cervical dysplasia/cancer in patients with inflammatory bowel disease (IBD). This systematic review was conducted to determine the risk of cervical abnormalities in patients with IBD and also estimate the comparative risk with respect to the general population. Methods: We searched various databases for studies which reported about rates of cervical intraepithelial neoplasia(CIN), cervical cancer or high risk HPV in IBD patients. We also extracted the rates of CIN, cervical cancer and high risk HPV in controls. Pooled prevalence of these lesions in IBD and relative risk in IBD patients in comparison to the healthy controls was estimated. We excluded studies which did not provide relevant data. All analysis were done in R version 4.1.1 using the meta and metafor packages. The random effects model was used with inverse variance approach for pooled prevalence and M-H method for calculation of relative risk. Results: We searched Embase, Medline and Pubmed and identified 522 relevant papers on 25th April 2022. Duplicates were removed and after initial screening, 44 papers were selected for full text screening. Eventually, 9 papers (5 case control and 4 cohort studies of 53,781 patients with IBD) were included in the quantitative synthesis. The pooled prevalence of CIN, cervical cancer and high risk HPV in the IBD population was 0.04 (0.01 - 0.11, I2= 100%). Patients with IBD were at a greater risk of cervical dysplasia/cancer when compared with healthy controls (relative risk 3.01, 1.44 - 6.31, I2= 100%). Conclusion: The patients with inflammatory bowel disease are at a heightened risk of developing cervical abnormalities like CIN,cervical cancer and high risk HPV lesions as compared to normal controls. These findings point to the importance of undergoing screening at regular intervals and significance of HPV vaccination in IBD patients in aiding to reduce the risk of developing cervical cancer.