Colposcopy-directed Biopsy Research Articles

Risk-stratified management of cervical high-grade squamous intraepithelial lesion based on machine learning.

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.

PAX1 methylation as a robust predictor: developing and validating a nomogram for assessing endocervical curettage (ECC) necessity in human papillomavirus16/18-positive women undergoing colposcopy

ObjectiveThe major challenge in routine endocervical curettage (ECC) among Human Papillomavirus (HPV) 16/18-positive patients is that only a small fraction benefit. Nevertheless, current reported models often overestimate the validity and necessity of ECC, making it difficult to improve benefits for patients. This research hypothesized that assessing paired boxed gene 1 methylation levels (PAX1m) and clinical characteristics could enhance the predictive accuracy of detecting additional high-grade squamous intraepithelial lesions or worse (HSIL +) through ECC that were not identified by colposcopy-directed biopsy (CDB).MethodsData from 134 women with HPV16/18 positivity undergoing CDB and ECC between April 2018 and April 2022 were collected and analyzed. Quantitative methylation-specific polymerase chain reaction (qMSP) was utilized to measure PAX1m, expressed as ΔCp. Univariate and multivariate regression analyses were conducted to screen variables and select predictive factors. A nomogram was constructed using multivariate logistic regression to predict additional HSIL + detected by ECC. The discrimination, calibration, and clinical utility of the nomogram were evaluated using receiver operating characteristic curves (ROC) and the calibration plot.ResultsAge (odds ratio [OR], 5.654; 95% confidence interval [CI], 1.131–37.700), cytology (OR, 24.978; 95% CI, 3.085–540.236), and PAX1 methylation levels by grade (PAX1m grade) (OR, 7.801; 95% CI, 1.548–44.828) were independent predictive factors for additional detection of HSIL + by ECC. In HPV16/18-positive women, the likelihood of additional detection of HSIL + through ECC increased with the severity of cytological abnormalities, peaking at 43.8% for high-grade cytological lesions. Moreover, when cytological findings indicated low-grade lesions, PAX1 methylation levels were positively correlated with the additional detection of HSIL + by ECC (P value < 0.001). A nomogram prediction model was developed (area under curve (AUC) = 0.946; 95% CI, 0.901–0.991), demonstrating high sensitivity (90.9%) and specificity (90.5%) at the optimal cutoff point of 107. Calibration analysis confirmed the model’s strong agreement between predicted and observed probabilities.ConclusionThe clinical nomogram presented promising predictive performance for the additional detection of HSIL + through ECC among women with HPV16/18 infection. PAX1 methylation level could serve as a valuable tool in guiding individualized clinical decisions regarding ECC for patients with HPV 16/18 infection, particularly in cases of low-grade cytological findings.

Comparative Study of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy and the Loop Electrosurgical Excision Procedure for the Treatment of Cervical High-Grade Squamous Intraepithelial Lesions.

The loop electrosurgical excision procedure (LEEP) is a common treatment for cervical intraepithelial neoplasia (CIN). Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) is a non-invasive modality that has been used for treating precancerous diseases and HPV infections. This comparative study evaluated the efficacy and safety of ALA PDT and the LEEP in the treatment of cervical high-grade squamous intraepithelial lesions (HSILs). Patient records were reviewed and HSIL patients with HPV infections (24-51 years old) who underwent PDT or LEEP treatment were selected. Efficacy was analyzed blindly based on HPV-DNA, cytology, and colposcopy-directed biopsy obtained at 6 months after treatment. Treatment-related discomfort and side effects were also analyzed. Cure rates of 88.1% and 70.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. HPV-negative conversion rates of 81.0% and 62.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. The overall lesion remission rate of the PDT group was 19% higher than that of the LEEP group. The incidence of side effects was much lower in the PDT group. These results show that ALA PDT is a feasible non-invasive treatment for cervical HSIL.

Efficacy and Safety of 5-Aminolevulinic Acid Photodynamic Therapy for Treating Cervical and Vaginal Intraepithelial Neoplasia.

Persistent HPV infections may cause cervical and vaginal intraepithelial neoplasia (CIN and VaIN). Traditional methods might destroy the structure and function of the cervix. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive targeted therapy. This study aims to evaluate the efficacy and safety of ALA-PDT for CIN and VaIN and the clearance of HPV. A retrospective study of 303 patients who confirmed CIN or VaIN and received ALA-PDT was conducted. All the patients were followed up at six and twelve months after treatment and then annually thereafter. The effect was evaluated through HPV genotyping, a cytology test, and colposcopy-directed biopsy if necessary. After ALA-PDT, the remission rates for CIN 2, CIN 3, VaIN 2, and VaIN 3 were 90.6%, 88.5%, 87.3%, and 77.8%. For CIN 1, the remission rate at the six-month follow-up was 93.1%. The total HPV clearance rates were 72.5% at the six-month follow-up and 85.7% at the 12-month follow-up. The most common adverse event was vaginal discharge. No severe adverse effect was observed. ALA-PDT is an effective and safe treatment for all grades of CIN and VaIN and is helpful in clearing HPV with minimal side effects. This treatment may not influence fertility and delivery.

The efficacy and safety of local 5-aminolevulinic acid-based photodynamic therapy in the treatment of cervical high-grade squamous intraepithelial lesion: a single center retrospective observational study.

Typical treatments for cervical high-grade squamous intraepithelial lesion (HSIL) are invasive procedures. However, these procedures often come with several severe side effects, despite their positive effects on cervical HSIL. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive treatment that has been successfully used to treat cervical low-grade squamous intraepithelial lesion (LSIL). In this study, we aimed to further investigate the clinical efficacy and safety of ALA-PDT in the treatment of patients with cervical HSIL. A total of 40 patients aged 20 - 41 years with cervical HSIL and high-risk Human Papilloma Virus (HR-HPV) infections were enrolled in this retrospective study from January 2019 to December 2022. Patients were treated with six times of ALA-PDT at intervals of 7-14 days. Three months after the treatment, the efficacy was evaluated through HPV genotyping and cervical cytology examination. If the cytological result was worse than ASC -US, the patient underwent colposcopy-directed biopsy immediately. Otherwise, patients would receive rigorous follow-up observation. Three months after receiving ALA-PDT treatment, 65% (26/40) of cervical HSIL patients at our center showed complete regression (cytological result: normal; HR-HPV: negative). This rate increased to 82.5% (33/40) at the 12-month follow-up. None of the patients experienced disease progression after ALA-PDT therapy. The risk of persistent HR-HPV infection was 32.5% (13/40) at the 3-month follow-up after ALA-PDT. Multivariate analyses identified cervical canal involvement as an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment. During the treatment of the 40 patients with ALA-PDT, there were no reports of severe adverse reactions. Only a limited number of patients experienced slight discomfort symptoms. ALA-PDT is safe and effective noninvasive therapy for patients with cervical HSIL and HR-HPV infections. It is particularly suitable for young women, who have been confirmed with cervical HSIL and have demand for fertility protection. Three months after ALA-PDT treatment, if a patient still has either ASC-US cervical cytological result and/or HR-HPV infection, rigorous observation is considered safe for her. Cervical canal involvement is an independent risk factor for persistent HR-HPV infection at the 3-month follow-up after ALA-PDT treatment.

Efficacy of Lidocaine Spray for Pain Reduction during Colposcopy-Directed Cervical Biopsies: A Randomized Controlled Trial.

Objectives: The objective of this study was to evaluate the efficacy of lidocaine spray in reducing the pain during colposcopy-directed cervical biopsy (CDB). Methods: From December 2017 to February 2019, 312 women undergoing CDBs were enrolled. The participants were randomized to three groups: group 1 (lidocaine spray), in which lidocaine spray was applied thoroughly to the cervix; group 2 (placebo), in which normal saline was applied thoroughly to the cervix; and group 3 (control), in which no anesthetic agent was applied to the cervix. Each woman completed a 10 cm visual analog scale to classify the subjective pain experience at three time points: baseline, immediately after biopsy, and 10 min after the procedure. The primary outcome of this study was the biopsy pain score. Results: The 312 enrolled women were randomly assigned to the three groups, amounting to 104 women per group. The clinical and pathological characteristics of the participants in all groups were comparable. The baseline, the biopsy, and the post-procedure pain scores were comparable among the three groups. There was a significant increase in the pain score from baseline to biopsy and from baseline to post-procedure in each group. The pain-score changes from baseline to biopsy in the lidocaine spray group significantly decreased when compared with the normal saline group (<0.001), and tended to decrease, though not significantly (p = 0.06), when compared with the control group. No complication with the intervention was observed. Conclusions: The application of lidocaine spray to the cervix has the benefit of reducing the pain associated with CDBs by a small amount. However, the intervention is safe and may be considered in nulliparous and/or overly anxious women undergoing the procedure.

Evaluation of the diagnostic performance of colposcopy in the detection of cervical high-grade squamous intraepithelial lesions among women with transformation zone type 3

BackgroundInaccurate colposcopy diagnosis may lead to inappropriate management and increase the incidence of cervical cancer. This study aimed to evaluate the diagnostic accuracy of colposcopy in the detection of histologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with transformation zone type 3 (TZ3).MethodsRecords from 764 patients with TZ3 who underwent colposcopy-directed biopsy and/or endocervical curettage in Putuo Hospital China between February 2020 and March 2023 were retrospectively collected. Colposcopy was carried out based on 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) and Colposcopy nomenclature. The diagnostic performance of colposcopy for identifying CIN2 + was evaluated compared with biopsies. The Kappa and McNemar tests were used to perform statistical analyses.ResultsAmong the study population, 11.0% had pathologic CIN2+. The relative sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of colposcopy for histologic CIN2 + were 51.2%, 96.5%, 64.2% and 94.1%, respectively. The senior colposcopists (80.6%) had a higher colposcopic accuracy to diagnose histologic CIN2 + than junior colposcopists (68.6%). In subgroup analyses, age group ≥ 60 years (70.3%) showed lowest diagnostic accuracy when compared with age groups of < 45 years (84.4%) and 45–59 years (74.9%).ConclusionOur findings suggest an increased risk of diagnostic inaccuracy of colposcopy in identifying CIN2 + in those ≥ 60 years of age with TZ3, and the accuracy of colposcopy is required to be further improved.

Cytologic Surveillance Versus Immediate Referral to Colposcopy for Women with a Cervical Cytology Diagnosis of ASC-US and LSIL in the Absence of HPV DNA Test

Background and Objectives: Cytology screening programmes decrease the risk of cervical cancer by detecting the precancerous changes. Treating these reduce the likelihood of developing invasive disease in future. The management strategies for severe precancerous changes are well established, however, this is not the case with minor cytological abnormalities like ASCUS or LSIL especially when a triage strategy like HPV testing is not easily available. This study aims to assess whether immediate referral to colposcopy is better than cytologic surveillance for women with a cervical smear diagnosis of ASC-US and LSIL in a context where HPV test is either unavailable or not affordable. Methods: A prospective study was conducted at a tertiary care hospital between January 2021 and November 2022. Total 126 women with a Pap smear report of ASC-US or LSIL were recruited to receive either cytologic surveillance (Group A) or immediate colposcopy (Group B), with 63 women in each group. Adherence to follow up and eventual histologic diagnosis of HSIL on colposcopically directed biopsy (CDB) and/or Loop electrical excision procedure (LEEP) were considered as the main study end-point. Results: Significantly more women defaulted from the cytologic surveillance group than the immediate colposcopy group (p=0.00001). In group B, using CDB and LEEP, 5 additional high-grade lesions were detected. However, the p value was not significant when compared with the cytologic surveillance group (p=0.360). Interpretation and Conclusions: Cytologic surveillance is fraught with a poor compliance rate. In the absence of HPV DNA test, minor cytologic abnormalities should undergo immediate colposcopy if follow up cannot be ensured. The high persistence rates of ASC-US and LSIL (41.18% and 35.71%), as well as the high progression rate of LSIL in the cytologic surveillance group, also underscore the necessity for these women to undergo immediate referral to colposcopy.

Clinical Characteristics and Detection Sensitivity of Cervical Cancer Screening in Vaginal Intraepithelial Neoplasia.

This study aimed to investigate the characteristics and screening history of vaginal intraepithelial neoplasia (VaIN) or vaginal cancer and compare the sensitivity of cytology and human papillomavirus (HPV) tests on the cervix against vaginal and cervical high-grade squamous intraepithelial lesion or cancer. This study included patients who underwent colposcopy-directed biopsy and were diagnosed with VaIN or vaginal cancer from February 2013 to November 2022. Clinical information was obtained from the medical records of the department. Statistical analysis was performed on SPSS 26.0 (IBM Corp, Armonk, NY) using t test, chi-square, and Fisher exact tests. A total of 1,166 patients were included in this study. The median age of VaIN2+ patients was 50.5 years, whereas VaIN1 reported a median age of 42.1 years old, p < .001. This study reported that VaIN was significantly and positively correlated with cervical lesions (r = 0.244). The high-risk HPV (hr-HPV) detection rate was 88.2% (858/973) in VaIN and 95.2% in VaIN2+. Human papillomavirus 16 was the most prevalent HPV type in VaIN2+, which accounted for 54.9%, followed by HPV58 (19.5%), HPV52 (15.2%), HPV51 (12.2%), and HPV18 (11.0%). The sensitivity of hr-HPV and cytology tests on the cervix for detecting VaIN2+ was 94.7% and 83.4%, respectively. Both tests were not significantly different from detecting cervical intraepithelial neoplasia 2+. Human papillomavirus 16 is the dominant HPV type in vaginal precancer lesions. Cervical cancer screening has similar sensitivity for VaIN2+ as for cervical intraepithelial neoplasia 2+, with hr-HPV testing showing higher sensitivity than cytology.

Role of Colposcopy in Diagnosing and Differentiating Types of Cervical Intraepithelial Neoplasia

Background: Preventing cervical cancer hinges on accurately detecting and treating high-grade cervical intraepithelial neoplasia (CIN2+) in individuals referred due to abnormal cervical cytology. While colposcopy has been a cornerstone in this process, concerns have arisen regarding its accuracy in CIN detection and differentiation. This study aims to assess the role of colposcopy in diagnosing and distinguishing various grades of CIN in clinically suspected patients. Methods: A descriptive cross-sectional study was conducted in the Department of Obstetrics &amp; Gynaecology at Rajshahi Medical College Hospital, Rajshahi, over 12 months from February 2019 to February 2020. The study involved 110 women aged 20-70 years who presented with clinical symptoms indicative of precancerous cervical lesions. Initial evaluations included visual inspection with 5% acetic acid (VIA) and Reid colposcopy. Biopsy samples were collected from the identified lesions using the colposcope, and these samples underwent histopathological examination. The study compared the diagnostic accuracy of colposcopy, including sensitivity, specificity, positive predictive value, and negative predictive value. Results: Colposcopic evaluations revealed that 80% of the participants exhibited positive lesions (CIN), while 20% displayed negative lesions (normal cervix or cervicitis). Among the colposcopically positive lesions, 50% were graded as CIN-1, 29.5% as CIN-2, and 20.5% as CIN-3. Subsequent histopathological examination of the colposcopy-directed biopsies confirmed CIN or dysplasia in 44.5% of cases. Within this group, 36.7% had CIN-1, 34.7% had CIN-2, 12.2% had CIN-3, 10.2% had invasive squamous cell carcinoma, and 6.2% had carcinoma in situ. Colposcopy demonstrated a sensitivity of 83.7% in diagnosing CIN, with a specificity of 23%, resulting in an overall diagnostic accuracy of 55%. However, when differentiating high-grade CIN from low-grade lesions, colposcopy exhibited a high sensitivity of 92.3% and moderate specificity of 67.7%, with an overall diagnostic accuracy of 75%. Conclusion: This study concludes that colposcopy is highly sensitive in diagnosing CIN but has limited specificity in excluding patients with normal cervix or cervicitis. Nevertheless, it exhibits optimal sensitivity in differentiating CIN2+ and carcinoma in situ from low-grade lesions and maintains moderate specificity in excluding low-grade CIN. Colposcopy remains a valuable tool in preventing and managing cervical cancer, particularly in identifying high-risk lesions.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery for the treatment of vulvar squamous intraepithelial lesion

BackgroundVulvar squamous intraepithelial lesion (SIL) is a precursor lesion of vulvar squamous cell carcinoma. The current clinical treatments for vulvar SIL cause damage to the vulvar structure, chronic pain and psychological distress. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel, non-invasive therapy for intraepithelial lesions. The objective of this study was to compare the clinical efficacy and safety of ALA-PDT with local surgical resection for vulvar SIL. MethodsA total of 56 patients with vulvar SIL were enrolled in this retrospective study. Among them, 16 patients received local resection and 40 patients received ALA-PDT. HPV genotyping and ThinPrep cytologic test (TCT) were used to evaluate treatment efficacy. In addition, colposcopy-directed biopsy was performed in all patients at 3-month follow-up and in patients with positive high-risk human papillomavirus (HR-HPV) and/or abnormal TCT results during the follow-up. ResultsAt 3-month follow-up and in HSIL group the complete remission (CR) rate of the ALA-PDT group and surgery group was 90.6% (29/32) and 87.5% (14/16) (P = 1.000), respectively. The HPV clearance rate of the ALA-PDT group and surgery group was 45.2% (14/31) and 43.8% (7/16) (P = 0.927), respectively. The average numbers of ALA-PDT treatments were 5.34 for HSIL patients and 4.88 for LSIL patients, respectively. The CR rate of HSIL patients and LSIL patients was 90.6% (29/32) and 75.0% (6/8) (P = 0.550), respectively. The HPV clearance rate of HSIL patients and LSIL patients was 45.2% (14/31) and 37.5% (3/8) (P = 1.000), respectively. The ALA-PDT group showed similar clinical efficacy and milder adverse effects compared with the surgical group. ConclusionALA-PDT showed similar clinical efficacy as surgery in the treatment of vulvar SIL, but with milder adverse effects and maintaining the integrity of the vulvar structure.

Efficacy of thermal ablation for treatment of biopsy-confirmed high-grade cervical precancer among women living with HIV in Kenya.

The World Health Organization recommends thermal ablation (TA) as an alternative to cryotherapy within "screen-and-treat" cervical cancer programs in low- and middle-income countries (LMICs), including among women living with HIV (WLWH). Data on TA efficacy among WLWH are limited, however. We conducted a clinical trial to evaluate efficacy of TA for treatment of biopsy-confirmed cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3) among WLWH in Kenya. Nonpregnant HPV-positive WLWH age 25 to 65 years underwent colposcopy-directed biopsy, and same-day treatment with TA, if eligible. Women with biopsy-confirmed CIN2/3 at baseline had colposcopy-directed biopsies at 12 months to determine cure. A total of 376 participants underwent TA during the study period. At baseline, 238 (63.3%) had normal histology, 39 (10.4%) had CIN1, 15 (4.0%) had CIN2, 55 (14.6%) had CIN3, 7 (1.9%) had microinvasive cancer and 22 (5.6%) had indeterminate results. Twelve-month follow-up pathology results are available for 59 of 70 (84.3%) participants with CIN2/3 at baseline. Of these, 39 (66.1%, 95% CI 0.54-0.99) had successful treatment, defined as biopsy-confirmed CIN1 or normal findings, while 20 (33.9%, 95% CI 0.22-0.46) had treatment failure, defined as persistent biopsy-confirmed CIN2 or worse. Treatment failure was 23.1% (95% CI 0.17-0.46) and 39.9% (95% CI 0.23-0.51) among women with CIN2 and CIN3 at baseline, respectively. HIV-positive women with CIN2/3 have high rates of treatment failure at 1-year following thermal ablation. This highlights a significant limitation in the current WHO cervical cancer secondary-prevention strategy and calls for strategies to optimize cervical precancer treatment in this population.

Clinical Efficacy and Safety of AdV-tk Gene Therapy for Patients with Cervical Squamous Intraepithelial Lesion: A Prospective Study.

Cervical cancer is the fourth most common type of cancer for women in 2020, and many more women have cervical pre-cancerous lesion-squamous intraepithelial lesion (SIL). Early treatment of cervical SIL to reverse or delay its progression is an important approach to reduce the incidence of cervical cancer. The efficacy and safety of adenovirus-based vectors expressing the thymidine kinase gene (AdV-tk) in the treatment of multiple types of cancers shows promise for its use in gynecology. We aim to provide relevant clinical efficacy and safety data after introducing AdV-tk for the treatment of cervical SIL for the first time through this prospective study. We conducted a maximum of 6-sessions to administer AdV-tk gene therapy to 23 patients (mean age: 35 years old) with cervical low-/high-grade SIL (LSIL/HSIL) who were enrolled from August 2015 to April 2018 and analyzed the clinical characteristics and follow-up outcomes (mean follow-up period: 7.3 months). The present study consisted of 17 patients (73.9%) with cervical HSIL and six patients with LSIL confirmed by colposcopy-directed biopsy. We observed an overall histological remission and regression rate of 87.0% (20/23, 95% confidence interval [95%CI]: 73.2-100%, P<0.001) after AdV-tk gene therapy. Eight patients (34.8%) were detected with human papillomavirus (HPV) 16/18 subtypes and 13 patients were found to be positive with at least one of the other 13 high-risk HPV (HR-HPV) subtypes, while two patients did not have any of the 15 HR-HPV subtypes. The overall clearance rate of HR-HPV was 76.2% (16/21, 95%CI: 58.0-94.4%, P=0.016) after AdV-tk gene therapy. For safety evaluation, no severe complications were reported in any of the 23 patients. The most commonly reported symptom was fever in 52.2% (12/23) of patients and all symptoms were fully resolved after symptomatic treatment. Our data indicates that AdV-tk gene therapy has high efficacy and safety in the treatment of cervical SIL among gynecological patients. Our findings provide clinical evidence on the potential promotion and application of AdV-tk in the treatment of cervical SIL, and potentially for cervical cancer, among gynecological patients.

Self- and physician-collected high-risk human papillomavirus (HPV) testing to detect high-grade cervical lesions among Thai women

ObjectiveWe compared the performance of high-risk human papillomavirus (HPV) messenger RNA testing of physician- and self-collected specimens for detecting histological grade 2 or higher cervical intraepithelial neoplasia (CIN) among women...

Detection of cervical high-grade squamous intraepithelial lesions and assessing diagnostic performance of colposcopy among women with oncogenic HPV

BackgroundHPV screening tests may improve cervical cancer risk stratification and better guide decisions about follow-up with colposcopy/biopsy. This study aimed to estimate the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with oncogenic HPV types and evaluate the performance of colposcopy in the diagnosis of histologic CIN2 + at Putuo Hospital, Shanghai, China.MethodsThis cross-sectional survey was conducted from February 2020 to December 2022 among women who were referred to colposcopy. Women with high-risk (HR) HPV-positive, cytology testing and colposcopy-directed biopsy were included.ResultsUnivariate and multivariate analysis indicated that high-grade colposcopic impression ((OR, 17.61%, 95%CI: 11.54–26.85%) was associated with the highest risk for detecting CIN2+, followed by HSIL + cytology (OR, 6.90%, 95%CI: 3.56–13.37%) and HPV16/18 positive (OR, 2.91%, 95%CI: 2.12–3.99%). Overall, CIN2 + was detected in 14.6% of 2007 women. HPV16/18 had higher CIN2 + risks than other HR-HPV genotypes (30.1% vs. 10.2%, P<0.001). Among women with low-grade cytology, 24.1% had CIN2+, and the risks for HPV16/18 (58.2%) were higher than for other HR-HPV(16.8%). For those with high-grade cytology, there was no significant difference between HPV groups ( 75.0% vs. 72.9%, P > 0.05). The diagnostic performance of colposcopy in diagnosis of CIN2 + by senior and junior colposcopists was comparable.ConclusionsThe results indicated that referral to colposcopy is recommended in managing women with HR-HPV positive, and colposcopic impressions provide key clues for identification CIN2+.

The Value of Four-Quadrant Cervical Biopsy in Women with Different Colposcopic Impressions.

The aim of this study was to compare the diagnostic efficacy of colposcopic-directed biopsy and four-quadrant biopsy in detecting high-grade cervical intra-epithelial neoplasia (CIN). Women attending three women's clinics for routine cervical screening were recruited. Colposcopy was arranged for women with any cytologic abnormalities greater than atypical squamous cells of undetermined significance (ASCUS), two consecutive ASCUS results or positive HPV testing. During colposcopy, a cervical biopsy was taken from the most suspicious area, but more than one biopsy was allowed. Four-quadrant biopsies at 3, 6, 9 and 12 o'clock and an endocervical curettage were also taken in all cases. A total of 1522 colposcopies were performed in 1311 subjects from June 2010 to August 2017, with 118 cases of high-grade CIN diagnosed. Colposcopic-directed biopsy detected 50.8% of the 118 high-grade CIN, while four-quadrant biopsy detected 86.4% (p < 0.0001). Twenty-seven cases (22.9%) of high-grade CIN were diagnosed in women with normal or unsatisfactory colposcopy. Among the 64 cases with low-grade colposcopic impression, four-quadrant biopsy detected significantly more high-grade CIN (53 cases, 82.8%) than colposcopic-directed biopsy (35 cases, 56.3%) (p = 0.0011). Four-quadrant cervical biopsies should be considered for all women with an abnormal smear or positive HPV testing, especially in patients with low-grade/normal/unsatisfactory colposcopy.

Value of loop electrosurgical excision procedure conization and imaging for the diagnosis of papillary squamous cell carcinoma of the cervix.

Loop electrosurgical excision procedure (LEEP) conization and hysterectomy are performed for some patients with papillary squamous cell carcinoma (PSCC), whereas only hysterectomy is performed for others. We aimed to determine the optimal management for PSCC. Patients diagnosed with PSCC by colposcopy-directed biopsy between June 2008 and January 2020 who underwent LEEP conization and hysterectomy or only hysterectomy at our hospital were enrolled. Results of cervical cytology, high-risk human papillomavirus testing, transvaginal sonography, pelvic magnetic resonance imaging, LEEP, hysterectomy, and pathology testing of colposcopy-directed biopsy samples were analyzed. A total of 379 women were diagnosed with PSCC by colposcopy-directed biopsy; 174 underwent LEEP before hysterectomy and 205 underwent only hysterectomy. Patients underwent and did not undergo LEEP were aged 47 ± 11 years and 52 ± 11 years, respectively. Among women who underwent LEEP, the agreement between LEEP and hysterectomy pathology was 85.1%. For women who underwent only hysterectomy, the agreement between preoperative clinical staging and pathological staging after hysterectomy was 82.4%. For patients with preoperative imaging indicative of malignancy, the accuracy of LEEP for diagnosing and staging PSCC was 88.5%, whereas for the hysterectomy-only group, it was 86.2%. For patients without malignancy detected with imaging, the accuracy of LEEP for diagnosing and staging PSCC was 81.6%; however, for those who did not undergo LEEP, it was 70.0%. For women diagnosed with PSCC by colposcopy-directed biopsy, LEEP conization is necessary for an accurate diagnosis when imaging does not indicate cancer; however, LEEP is not necessary when imaging indicates cancer.

Correlation between Colposcopic Findings and Histopathological Results from Colposcopy Directed Biopsy in VIA(+VE) Cases

Background: Cervical cancer is a major global health problem, with a high burden in developing countries. Early detection and management of precancerous conditions, such as cervical intraepithelial neoplasia (CIN), can help to prevent the development of cervical cancer. Colposcopy, which involves the visualization of the cervix through optical instruments, is considered the gold standard for the diagnosis of cervical abnormalities. The aim of the study was to assess the correlation between colposcopy findings and histopathological results in cases where visual inspection of the cervix with acetic acid (VIA) was positive. Material &amp; Methods: This cross-sectional study was conducted at the Department of Gynecology, Institute of Child and Mother Health, Matuail, Dhaka, Bangladesh. The study duration was 1 year, from November 2017 to October 2018. Participants were recruited from the hospital’s gynecology outpatient department and included 95 women who had a positive VIA test. A Purposive consecutive sampling method was followed for the selection of the participants. Results: The study included 95 patients in Bangladesh who had a positive VIA test. The age distribution of the patients ranged from 25 to 60 years, with a mean age of 35.89±8.88 years. The majority of patients (85.3%) had acetowhite areas, followed by 11 (11.5%) punctuation and 3 (3.2%) mixed (acetowhite area and mosaicism). Histopathological findings revealed that one-third (33.6%) of patients had chronic cervicitis, with 36 (378.8%) having moderate dysplasia, 16 (16.8%) having mild dysplasia, 7 (7.5%) having invasive carcinoma, and 4 (4.2%) having chronic cervicitis with sq. metaplasia. Among the cases, the comparison between colposcopy-directed biopsy results and Colposcopy findings. It was observed that more than one-fourth of 24(29.7%) patients were chronic cervicitis in pure acetowhite area, 8(72.7%) in punctuation, and all patients were mild dysplasia in mixed (acetowhite area and mosaicism). Among 81 patients 53 patients presented with pre-cancerous lesions. The difference was statically significant (p&lt;0.05) in the study patients. Conclusion: Colposcopy, which involves the visualization of the cervix through optical instruments, was found to be an effective tool for the diagnosis of cervical abnormalities in these cases. These findings highlight the importance of colposcopy as a diagnostic tool for cervical abnormalities, particularly in resource-limited settings where access to other screening methods may be limited.

Efficacy of optical coherence tomography in the triage of women with minor abnormal cervical cytology before colposcopy.

To evaluate the efficacy of Optical Coherence Tomography (OCT) for detecting cervical lesions in women with minor abnormal cytology results (atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL)). A prospective study was conducted at gynecologic clinic from Mar 2021 to Sep 2021. The recruited women with cervical cytological findings of ASC-US or LSIL were inspected with OCT before colposcopy-directed cervical biopsy. The diagnostic performance of OCT, alone and in combination with high-risk human papillomavirus (hrHPV) testing were evaluated to detect cervical intraepithelial neoplasia of grade 2 or worse (CIN2+)/CIN3 or worse (CIN3+). The rate of colposcopy referral and the immediate risk of CIN3+ of OCT were calculated. A total of 349 women with minor abnormal cervical cytology results were enrolled. For detection of CIN2+/CIN3+, the sensitivity and NPV of OCT were lower than those of hrHPV testing (CIN2+: 71.3% vs. 95.4%, 89.0% vs. 91.1%, P < 0.001; CIN3+: 75% vs. 93.8%, 96.5% vs. 95.6%, P < 0.001), but the specificity, accuracy and PPV were higher than those of hrHPV testing (CIN2+: 77.5% vs. 15.6%, 75.9% vs. 35.5%, 51.2% vs. 27.3%, P < 0.001; CIN3+: 69.4% vs. 13.6%, 69.9% vs. 20.9%, 19.8% vs. 9.9%, P < 0.001). OCT combined with hrHPV testing (CIN2+: 80.9%; CIN3+: 72.6%) showed higher specificity than that of OCT alone (P < 0.001). The colposcopy referral rate base on OCT classification was lower than that based on hrHPV testing (34.7% vs. 87.1%, P < 0.001). Patients with hrHPV-positive ASC-US and hrHPV-negative LSIL cytology, the immediate CIN3+ risk in OCT negative cases was less than 4%. OCT alone or combination with hrHPV testing shows good performance for detecting CIN2+/CIN3+ in patients with ASC-US/LSIL cytology. OCT is an effective method for colposcopy triage in women with hrHPV-positive ASC-US and hrHPV-negative LSIL cytology.

Performance of screening tools for cervical neoplasia among women in low- and middle-income countries: A systematic review and meta-analysis.

To evaluate the performance of visual inspection with acetic acid (VIA) testing, visual inspection with Lugol's iodine (VILI), primary HPV testing, and conventional Pap smear in detecting CIN2+ among non-pregnant women aged 30-65 in LMICs between 1990 and 2020. Systematic review and meta-analysis. Low- and middle-income countries, non-pregnant women aged 30-65. CENTRAL (Cochrane Library), CINAHL, Embase, Global Health, PubMed, and Web of Science databases were systematically searched to identify studies evaluating the performance of cervical cancer screening methods in LMICs. A diagnostic test accuracy meta-analysis was conducted to evaluate the performance of 4 screening methods in detecting CIN2+ relative to biopsy or cytology reference standards. Pooled statistics for sensitivity, specificity, diagnostic odds ratios, and summary receiver operating characteristic curves were determined for each method. Subgroup analyses were performed to examine whether there was variation in performance based on different reference standards for defining CIN2+, specifically: colposcopy-directed biopsy, biopsy alone, colposcopy alone, or liquid-based cytology. Eighteen studies were identified through systematic review. Twelve studies were included in meta-analysis; 11 were cross-sectional and 1 was a randomized controlled clinical trial. The remaining six of the eighteen studies were inclided in a narrative syntehsis. Pooled estimates for sensitivity for VIA, VILI, primary HPV testing, and conventional Pap smear were 72.3%, 64.5%, 79.5%, and 60.2%, respectively; pooled estimates for specificity were 74.5%, 68.5%, 72.6%, and 97.4%, respectively; the diagnostic odds ratios were 7.31, 3.73, 10.42, 69.48, respectively; and the area under the summary receiver operating characteristic curves were 0.766, 0.647, 0.959, and 0.818, respectively. Performance of the screening method varied based on the reference standard used; pooled estimates using either colposcopy-directed biopsy or biopsy alone as the reference standard generally reported lower estimates; pooled estimates using either colposcopy alone or liquid-based cytology as references reported higher estimates. This meta-analysis found primary HPV testing to be the highest performing cervical cancer screening method in accurately identifying or excluding CIN2+. Further evaluation of performance at different CIN thresholds is warranted.