Squamous Intraepithelial Lesions Research Articles

Impact of CD40 gene polymorphisms on the risk of cervical squamous cell carcinoma: a case-control study

BackgroundCervical cancer is the fourth most common cancer among women worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical cancer risk. Therefore, we aimed to investigate the correlation between single nucleotide polymorphisms (SNPs) of the CD40 gene and susceptibility to cervical squamous cell carcinoma (CSCC) in a population from the northeastern Han Chinese population.MethodsThe three SNPs (rs1800686, rs3765459, and rs4810485) of the CD40 gene were analyzed by multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods in 421 patients with CSCC, 594 patients with high-grade squamous intraepithelial lesions (HSIL), and 504 healthy females. Multivariate logistic regression analysis was used to analyze the potential relationship between CD40 gene polymorphisms and CSCC, or HSIL.ResultsOur research results showed the AA genotype of rs1800686 had a protective effect on CSCC in comparison to the GG genotype and AG+GG genotypes (AA vs. GG: p = 0.0389 and AA vs. AG+GG: p = 0.0280, respectively). After FDR correction, the results were still statistically significant (p = 0.0389 and p = 0.0389, respectively). Similarly, rs3765459 showed a reduced risk association for CSCC in the codominant and recessive models (AA vs. GG: p = 0.0286 and AA vs. AG+GG: p = 0.0222, respectively). Significant differences remained after FDR correction (p = 0.0286 and p = 0.0286, respectively). However, these differences were no longer significant after the Bonferroni correction. In addition, the genotypes for the rs4810485 polymorphisms were associated with parity of the patients with CSCC. The genotypes for the rs3765459 polymorphisms were significantly correlated with the D-dimer of the patients with CSCC. The 3 SNPs genotypes of the CD40 gene were closely related to the squamous cell carcinoma antigen (SCC) of the patients with HSIL.ConclusionsThe CD40 gene may play a role in the occurrence and development of CSCC.

Cervical Cytology Findings in Renal Transplant Patients and Comparison of These Findings with Normal Population

Long-term immunosuppressive therapy increases the likelihood of renal transplant patients developing cervical cancer. We aimed to analyze the results of cervical cytology in renal transplant patients, compare these findings to those of the normal population, and determine the risk factors linked to the development of squamous intraepithelial lesions. Our analysis involved a retrospective study of hospital records from January 2000 to April 2018, encompassing 140 female renal transplant patients. A control group of 280 women with normal health status was selected and matched based on age and the cervical cytology procedure. The cervical cytology findings of the patients were re-evaluated using the Bethesda 2014 criteria. Of the total of 420 patients, 37 patients had epithelial cell abnormalities; including 32 (86.5%) patients in the renal transplant group and 5 (13.5%) control group (p ≤ 0.001). Sixty-two patients had infections; including 44 (71%) patients in the renal transplant group and 18 (29%) control group (p ≤ 0.001). We revealed that the development of squamous intraepithelial lesions was associated with factors such as having an immunologic disease as the primary renal disease, undergoing re-transplantation, and the presence of acute rejection (p ≤ 0.05). Cervical cytology screening plays a crucial role in detecting preinvasive lesions. The incidence of epithelial cell abnormalities is significantly higher in renal transplant patients compared to the normal population. Regular cervical cytology follow-up is vital for the early detection and prevention of cervical cancer progression in transplant recipients.

Is the Anal Component of the Anogenital HPV-Related Disease Overlooked During the Surveillance of Patients Treated for Cervical Intraepithelial Neoplasia?

To investigate the anal component of the anogenital Human Papillomavirus (HPV) related disease during surveillance of patients treated for cervical intraepithelial neoplasia (CIN). Patients were analyzed within two groups according to the histopathological examination of the cervical biopsies: Low-Grade Squamous Intraepithelial Lesion (LSIL) and High-Grade Squamous Intraepithelial Lesion (HSIL) groups. Anal specimens were also collected in the first-year follow-up visit. All patients had cervical high-risk HPV (HR HPV) infection at admission. At the first-year follow-up, positive HR HPVs were found in 47% of cervical samples. Despite this clearance, the anal HPV infection rate after the first year was 42.5% and 39.6% in LSIL and HSIL groups. Amongst the HSIL group, anal HR HPV positivity was observed in 29.6% of cases without any cervical HPV infection. A group of women cured of high-grade lesions have ongoing anal HPV infection. It is reasonable to propose that detecting anal HPV could impact the patient's treatment process. Therefore, prospective studies are needed to investigate this group of women's clinical outcomes and define the clearance rate of cervical HPV infection when anal HPV persists.

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.

Efficacy and pregnancy outcomes of focused ultrasound for cervical high-grade squamous intraepithelial lesions

Objective To investigate the efficacy and adverse effects of focused ultrasound (FU) in the treatment of high-grade squamous intraepithelial lesions (HSIL) and follow up on pregnancy outcomes in patients. Methods This retrospective study recruited 57 patients aged 20–40 years with cervical HSIL combined with HR-HPV infection who received FU treatment between September 2019 and April 2022. Clinical data of the patients were obtained from hospital records. HSIL cure rate and cumulative HR-HPV clearance rate were assessed after treatment. Patients were followed up on fertility and pregnancy outcomes after treatment by telephone interviews until April 1, 2023. Results During a 6-month follow-up, the HSIL cure rate was 73.7%, and a statistical difference between CIN2 and CIN3 (75.6% vs. 66.7%, p = 0.713) was not present. HSIL -recurrence was not observed during the follow-up period, and the median follow-up duration was 12 months. The cumulative HR-HPV clearance rates at the 6- and 12-month follow-ups were 56.1% and 75.4%, respectively. The median clearance time of HR-HPV was 6 (95% confidence interval, 5.46–6.54) months. The clearance rate was higher in HPV16/18 than in non-HPV16/18 (86.7% vs. 62.9%, p = 0.038). After treatment, the successful pregnancy rate in patients with fertility intentions and spontaneous abortion rate were 73.9% and 5.9%, respectively. Preterm birth, preterm premature rupture of membranes, or low-birth-weight infants were not observed. Conclusion FU treatment can regress HSIL and accelerate HR-HPV clearance in young women of childbearing age with cervical HSIL associated with HR-HPV infection, and has no significant adverse effects on pregnancy outcomes.

Are HPV-negative lesions concerned for the introduction of primary HPV testing for cervical cancer screening in Japan?

In Japan, primary human papilloma virus (HPV) testing has not been introduced for cervical cancer screening due to concerns that HPV-negative lesions may be missed and a lack of Japanese data. The purpose of this study was to evaluate the validity of primary HPV testing in Japan by analyzing cervical intraepithelial neoplasia 2 (CIN2) or more/high-risk HPV- (CIN2+/hrHPV-) cases in cervical cancer screening. Data from 35 525 cervical cancer screenings with HPV testing and cervical cytology from 2011 to 2019 in Saga City, Japan, were reviewed. The cases with low-grade squamous intraepithelial lesion (LSIL+)/hrHPV- were analyzed in detail. The results of the 35 525 examinees were as follows: 31 123 were negative for intraepithelial lesion or malignancy (NILM)/hrHPV-, 2612 were NILM/hrHPV+, 262 were atypical squamous cells of undetermined significance (ASC-US)/hrHPV-, 213 were ASC-US/hrHPV+, 291 were LSIL+/hrHPV-, and 1024 were LSIL+/hrHPV+. Of the 256 LSIL+/hrHPV- examinees for whom histology was available, CIN2+ were CIN2 9.4% (24/256), CIN3 3.9% (10/256), cervical adenocarcinoma 0.4% (1/256), uterine corpus cancer 1.2% (3/256), and uterine sarcoma 0.4% (1/256). Overall, the rate of LSIL+/hrHPV- was 0.82% (291/35.525), 0.1% (36/35525) of which were cervical lesions with CIN2+. Only one cervical adenocarcinoma was detected, but gastric-type adenocarcinoma was not included. HPV-negative CIN2+ or cervical adenocarcinoma is not a concern for the introduction of primary HPV screening in Japan. Primary HPV testing in cervical cancer screening is considered a feasible method that can be used in Japan, although an algorithm suitable for Japan and a national-level management system need to be established.

Clinical and epidemiological features of high-risk human papillomavirus infection in patients with cervical intraepithelial lesions

ObjectiveIn this study, we analyzed the clinical and epidemiological features of high-risk human papillomavirus (HR-HPV) infection in patients with cervical intraepithelial lesions.MethodsRetrospective analysis was performed on the clinical data of 240 cases of histologically confirmed cervical squamous intraepithelial lesions to determine any correlation between HPV infection characteristics, age distribution, and cervical epithelial lesions.ResultsPatients between the ages of 31 and 40 with cervical intraepithelial lesions were more likely to have high-grade squamous intraepithelial lesions (HSIL; 40.7%) than low-grade squamous intraepithelial lesions (LSIL; 31.3%) (P < 0.05). In patients with HSIL, HR-HPV16, HR-HPV33, and HR-HPV52 were the most common types of HPV infection, while in patients with LSIL, HR-HPV16, HR-HPV52, and HR-HPV58 were the most common types of HPV infection. The highest percentage of single infections occurred in the HSIL group (69.6%), followed by the LSIL group (68.8%). HSIL was present in a significant number of patients (28.6%) aged 30 years and above who tested positive for 12 HPV types but negative for TCT.ConclusionThe prevalence of HSIL is greatest in younger patients. Patients with cervical epithelial lesions typically have a single infection of a high-risk HPV genotype—HR-HPV16, HR-HPV33, HR-HPV52, or HR-HPV58. Patients aged 30 years and above who test positive for one of 12 types of HPV but negative for TCT are at increased risk for developing HSIL. In order to detect cervical lesions early and begin treatment without delay, colposcopy should be performed regardless of whether or not a high-risk HPV infection is present.

Synchronous High-Grade Squamous Intraepithelial Lesion of the Fimbria of the Fallopian Tube in a 51-Year-Old Woman with Invasive Squamous Cell Carcinoma of the Uterine Cervix.

Primary squamous cell carcinoma or squamous intraepithelial lesion of the fallopian tube is a very rare finding with only a small number of cases worldwide. We describe the case of a 51-year-old woman, undergoing an abdominal hysterectomy after the diagnosis of an HPV-associated invasive squamous cell carcinoma of the uterine cervix with the unexpected detection of an HPV16-positive high-grade squamous intraepithelial lesion of the fimbria of the right fallopian tube in the resection specimen. The finding of an isolated, HPV-associated squamous intraepithelial lesion in the fallopian tube raises the question of a de novo development in this body compartment (after exclusion of a continuous metastatic spread from the uterine cervix) by taking a virus-associated field effect into account and should encourage the inclusion of this possibility when examining the fallopian tube in a routine setting.

Abnormal Pap smear among pregnant women - Feasibility of opportunistic cervical screening.

The uptake of cervical cancer screening is poor, especially in developing countries. Thus, pregnancy represents a good opportunity to have the test done. The aim of this study is to determine the prevalence of abnormal Pap smear among pregnant women during their antenatal check-ups. A prospective study involving five hundred and ninety-six women was recruited over a 1-year duration from 15th January 2018 until 14th January 2019 in a tertiary referral center, in Malaysia. Pap smears were performed on all consented pregnant women using liquid-based cytology and the results were obtained to evaluate the prevalence of abnormal Pap smear during pregnancy. Maternal risk factors associated with abnormal Pap smear were identified and the outcomes of abnormal Pap smear were followed up. A total of 670 participants were approached and 596 participants agreed to participate, giving a response rate of 89.0 %. Therefore, 587 participants were available for analysis. There were nine unsatisfactory smears (1.5 %). The prevalence of premalignant lesions reported on p % ap smear was 0.8 %. Three respondents had atypical squamous cells of undetermined significance (ASCUS) (0.5 %) and two respondents had low-grade squamous intraepithelial lesions (LSIL) (0.3 %). Almost one-third (30.3 %) of respondents had an infection and 24 (4.1 %) smears were reported as reactive changes associated with inflammation. Respondents between the age of 20-30 years old had a significant association with an abnormal pre-cancerous smear (p=0.000) as well as nulliparity (p=0.0.40). There was no significant association between height, weight, BMI, sexual partner, age of first intercourse, smoking habit, history of sexually transmitted disease and history of abnormal Pap smear. The prevalence of abnormal pre-cancerous smears during pregnancy is low. However, it is desirable to perform cervical screening as it provides an opportunity to no screening at all.

Overtreatment in the see-and-treat approach for high-grade squamous cervical cytology.

To evaluate overtreatment with the 'see-and-treat' approach in patients with high-grade squamous cervical cytology, and identify the clinical factors associated with overtreatment. Patients with high-grade squamous intra-epithelial lesion (HSIL) cytology undergoing colposcopy and loop electrosurgical excision procedure (LEEP) in a single visit or the 'see-and-treat' approach from January 2005 to December 2019 were reviewed retrospectively. The overtreatment rate and complications following LEEP were explored. In total, 220 cases were identified. The overtreatment rate was 11.4%, and surgical complications were haemorrhage (n=3, 1.36%) and infection (n=9, 4.09%). On univariable analysis, factors associated with overtreatment were current cytological result and colposcopic impression. On multi-variable analysis, current cytological result of non-HSIL compared with HSIL/cancer, and colposcopic diagnosis of low-grade lesion or normal compared with high-grade lesion or cancer had adjusted odds ratios of 13.81 [95% confidence interval (CI) 1.23-155.20; p=0.033] and 3.58 (95% CI 1.32-9.74; p=0.013), respectively. The overtreatment rate with the 'see-and-treat' approach was 11.4%. Independent factors associated with overtreatment were current cervical cytological result of non-HSIL, and low-grade or normal colposcopic diagnosis.

High Specificity of HPV Cell-Free DNA Tests in Persons With HIV for the Detection of HPV-Related Cancer.

Persons with HIV (PWH) experience high rates of human papillomavirus (HPV)-associated cancers compared with the general population. Plasma HPV cell-free DNA (cfDNA) tests are sensitive in patients with known HPV-associated cancers. It is not known whether these tests can screen for invasive cancers in populations with high burdens of nonmalignant HPV disease such as PWH. It was not known whether HPV infection and/or noninvasive anal high-grade squamous intraepithelial lesions (HSIL) alone in this population would result in detectable HPV cfDNA, which would result in a high number of false positives if HPV cfDNA is used to screen for invasive cancers. We conducted a prospective study of PWH in 2 cohorts: 20 without anal HSIL and 20 with anal HSIL. We tested anal and vaginal swabs for HPV infection, and HPV genotyped the biopsies of anal HSIL. Finally, we performed HPV cfDNA droplet digital polymerase chain reaction to test for HPV16/18/33 from plasma samples. In the combined cohorts, the median age was 56 years, 12.5% were cisgender women, and none had detectable HIV. In total, 84.6% had prevalent anovaginal HPV infection, including 10 participants with HPV16, 13 with HPV18, and 2 with HPV33 infections. Five and 2 participants had HPV16 and HPV33 detected in anal HSIL, respectively. Despite the high prevalence of HPV infection and anal HSIL, no participant had HPV16/18/33 detectable cfDNA by droplet digital polymerase chain reaction. These results provide a strong rationale for investigating the use of HPV cfDNA in a screening setting for suspected HPV-related invasive cancers in PWH.

Does Absence of Transformation Zone Component in Anal Cytology Sample Affects Detection of Squamous Intraepithelial Lesions?

Does Absence of Transformation Zone Component in Anal Cytology Sample Affects Detection of Squamous Intraepithelial Lesions?

Cervical Papanicolaou Smear Test Screening among Patients Visiting the Outpatient Department of Gynaecology of a Tertiary Care Centre.

Carcinoma cervix is the second most common cause of death in women worldwide and the most common cause in developing countries. Cervical cancer is considered a preventable gynaecological problem as it has a long premalignant stage which can be detected by exfoliative cytology like papanicolaou smear test. The papanicolaou smear test is a simple, safe, non-invasive, and low-cost effective method for screening cervical cancer in developing countries like Nepal. The aim of the study was to find out the prevalence of cervical papanicolaou smear test screening among patients visiting the Outpatient Department of Gynaecology of a tertiary care centre. A descriptive cross-sectional study was conducted among patients visiting the Department of Gynaecology of a tertiary care centre after obtaining ethical approval from the Institutional Review Committee. Data from 14 April 2021 to 22 October 2022 were collected between 11 May 2023 to 26 May 2023 from the hospital records. Papanicolaou smear tests among the age group of 21 years up to 70 years were included in the study. Convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Among 11,173 patients, papanicolaou smear test was done in 572 (5.12%) (4.71-5.53, 95% Confidence Interval). Negative for intraepithelial lesion was the most common cytological pattern seen in 518 (90.55%) patients. The low-grade squamous intraepithelial lesion was the most common among abnormal epithelial cells seen in 29 (5.07%). The prevalence of cervical papanicolaou smear test among patients visiting the Outpatient Department of Gynaecology was found to be similar to other studies done in similar settings. cervical cancer; cytology; papanicolaou smear.

The impact of transformation zone representation on the frequency of abnormal cervical cytological results

ObjectiveTo compare the frequency of abnormal cervical cytological results with and without representation of the transformation zone (TZ) in a medium-sized city in Brazil according to the Bethesda categorization. MethodsWe performed an analytical observational study evaluating cytological results over 15 years from conventional smears collected within the Public Brazilian Health System in Araçatuba, Brazil. Tests were stratified by age and cytological result according to Brazilian guidelines and the Bethesda System. ResultsThere were 261,881 examinations, 159,251 with and 102,630 without TZ representation. The global frequency of abnormal results was higher in smears with TZ representation (crude odds ratio [OR] 4.03; 95% confidence interval [CI] [3.71–4.38]). Considering only women between 25 and 64 years (the target of the national guidelines), there were higher results for high-grade squamous intraepithelial lesions (OR 11.54; 95% CI 6.74–19.78), low-grade squamous intraepithelial lesions (OR 2.82; 95% CI 2.17–3.67) atypical squamous cell in which high-grade intraepithelial lesion cannot be excluded (OR 6.90; 95% CI 4.91–9.66) and atypical squamous cell of undetermined significance (OR 3.53; 95% CI 3.11–4.01) among cases with TZ representation. ConclusionSamples with TZ representation were associated with higher rates of abnormal results. Health professionals should be regularly trained to understand the weakness of cytological examinations when the TZ is not represented, especially in developing countries.

Prevalence of human papillomavirus infection in abnormal pap smears.

This study was undertaken to study the prevalence of human papillomavirus (HPV) infection using the polymerase chain reaction (PCR) technique in abnormal cervical pap smears and to correlate the different cytological results with HPV infection. A total of 1788 cervical pap smears of women more than 30 years of age conducted over a period of 1 year 3 months (June 2015-August 2016) were screened by liquid-based cytology. High-risk (HR)-HPV testing was performed by PCR in abnormal lesions. Inflammatory smears and some atypical squamous cells of undetermined significance (ASCUS)-reactive cases were excluded from HPV testing. Histopathological correlation was done wherever possible. The overall prevalence of the intraepithelial lesions/malignancy was ASCUS. (ASCUS) - 79 (4.42%), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) - 10 (0.56%), low-grade squamous intraepithelial lesion (LSIL) - 26 (1.45%), high-grade squamous intraepithelial lesion (HSIL) - 15 (0.84%), squamous cell carcinoma - 5 (0.28%), and adenocarcinoma - 1 case (0.06%). Overall, 136 (7.60%) samples were classified as abnormal. Seventy-seven samples were included for HR-HPV testing - 20 ASCUS, 10 ASC-H, 26 LSIL, 15 HSIL, and 6 malignant cases. A control group of ten samples with normal cervical cytology within the normal limit (Control) (WNLc) was tested for HR-HPV. HR-HPV was detected in 20% of samples of the WNLc group, 45% of the ASCUS group, 70% of the ASC-H group, 73.07% of the LSIL group, 86.67% of the HSIL, and 83.34% of the samples in the malignant group. Overall, HR-HPV was detected in 68.83% of abnormal cervical pap smears. Our study shows that the percentage of HR-HPV-positive case increases with the severity of cytologic morphology. HPV had 4 times higher positivity in squamous intraepithelial lesion as compared to ASCUS.

Spectrum of cervicovaginal Pap smears in newly established tertiary care medical institute.

We undertook this study to find out the spectrum of the cervical smear pattern along with the clinical profiles of patients who underwent cervical Papanicolaou (Pap) smear evaluation in our newly started tertiary care center. We also tried to find the possible clinical cause for unsatisfactory smears and factors for epithelial cell abnormality. The present study was a retrospective observational study. Pap smears cases with their clinical findings mentioned on the requisition form and cytopathology observations were retrieved from the archives of the department of pathology. Fisher's exact test was used for statistical analysis. Five hundred and ninety-four cases were included in the study. The most common age group was 36- 40 years. White discharge per vaginum was the most common clinical presentation. The negative for squamous intraepithelial lesions or malignancy was the most common interpretation (86.87%). Cervical erosion had statistically significant associations with unsatisfactory smears, while bacterial vaginosis had with satisfactory smears. Epithelial cell abnormality was seen in 4.62% patients. We observed a statistically significant association of cervical mucoid discharge, and inflammation with "no epithelial cell abnormality" cases, while postmenopausal bleeding was associated with "epithelial cell abnormality" cases. In the presence of clinical factors like cervical erosion, which may affect the quality of Pap smear, proper sampling techniques are to be used by health-care providers. The careful evaluation of Pap smears, especially in cases of cervical mucoid discharge, postmenopausal bleeding, and inflammatory smears is required to ensure that epithelial cell abnormalities are not overlooked.

Extensive lesions and a positive cone margin are strong predictors of residual disease in subsequent hysterectomy following conization for squamous intraepithelial lesion grade 2 or 3 study design

BackgroundThis study aimed to determine the predictive factors for post-conization of residual disease in subsequent hysterectomy for cervical intraepithelial neoplasia grade 2 or 3.MethodsThis retrospective study included 267 patients with histologically confirmed cervical intraepithelial neoplasia grade 2 or 3 who underwent hysterectomy within 7 months after conization. Clinical data (e.g., age, menopausal status, gravidity, parity, type of transformation zone, conization method) as well as pathological data pertaining to conization and hysterectomy were collected from medical records. A logistic regression model was used to analyze the relationship between the variables and risk of residual lesions in hysterectomy samples.ResultsOverall, 70 (26.2%) patients had residual lesions in their hysterectomy specimens. Univariate analyses revealed that age ≥ 50 years (p=0.019), endocervical gland involvement(p=0.013), positive margin(p < 0.001), and involvement of 3–4 quadrants(p < 0.001) were risk factors for residual lesions. Conversely, postmenopausal status, gravidity ≥ 3, parity ≥ 2, loop electrosurgical excision procedure, and type III transformation zone were not risk factors for residual lesions. A positive margin(p < 0.001) and multiple-quadrant involvement(p < 0.001) were identified as independent risk factors for residual lesions on multivariate analysis.ConclusionsMultiple-quadrant involvement and a positive cone margin were reliable predictive factors for residual disease. Total hysterectomy or repeated cervical conization should be considered for patients with these two risk factors. The identification of high-risk patients with extensive lesions by colposcopic examination before conization is indispensable, as it will enable surgeons to perform conization with consideration of risk factors and possibly improve the approach used for the excisional procedure. For high-risk patients, colposcope-guided cold-knife conization is preferred when resources permit.

Detection rate and clinical characteristics of vulvar squamous intraepithelial lesion

Objective: To explore the detection rate, clinical characteristics of vulvar squamous intraepithelial lesion (SIL). Methods: Women diagnosed with vulvar high-grade squamous intraepithelial lesions (HSIL) through colposcopy-guided biopsy from January 1, 2018 to August 31, 2022 in Obstetrics and Gynecology Hospital of Fudan University were included in a 1∶1 ratio with patients diagnosed with vulvar low-grade squamous intraepithelial lesions (LSIL) during the same period. Clinical characteristics including human papillomavirus (HPV) infection rate, genotype, cytology result, colposcopy impression, and lesion location were retrospectively analyzed. Results: (1) The proportion of vulvar SIL detected by colposcopy-guided biopsy increased annually from 2018 to 2022, with rates of 1.64% (740/45 057), 2.34% (1 110/47 402), 2.68% (1 108/41 335), 3.26% (1 536/47 078), 3.31% (667/20 155), with an average rate of 2.57% (5 161/201 027). (2) A total of 1 096 cases of vulvar HSIL and 1 096 cases of vulvar LSIL were included. The overall infection rate of HPV was 92.7% (1 993/2 150), with higher infection rate in vulvar HSIL patients than that in vulvar LSIL patients [96.0% (1 012/1 054) vs 89.5% (981/1 096); χ2=33.62, P<0.001]. Among vulvar HSIL patients, the common HPV genotype from high to low were HPV 16 (66.7%), HPV 52 (14.3%), and HPV 58 (10.0%). For vulvar LSIL patients, the most common HPV genotype were respectively HPV 16 (24.9%), HPV 6 (20.1%) and HPV 52 (17.1%). The overall sensitivity rate of cytology was 53.6%, with no significance difference between vulvar LSIL and HSIL groups (54.3% vs 52.9%; χ2=0.40, P=0.526). The accuracy of colposcopy impression for vulvar HSIL was lower than that for vulvar LSIL [40.2% (163/405) vs 81.7% (380/465); χ2=158.72, P<0.001]. About 57.3% (1 257/2 192) of the patients had concomitant cervical and vaginal lesions, with a higher rate in vulvar HSIL group than that in vulvar LSIL group [62.6% (686/1 096) vs 52.1% (571/1 096); χ2=24.67, P<0.001]. Unifocal lesion was the main type, with no significance difference between vulvar LSIL and HSIL groups [81.4% (381/468) vs 82.5% (386/468); χ2=0.18, P=0.671]. The most common lesion locations were the posterior commissure, followed by labia minora, vaginal vestibule, labia majora, perianal and clitoris. Conclusions: The detection rate of vulvar SIL under colposcopy is about 3%, and the infection rate of HPV is 92.7%. Vulvar SIL, especially vulvar HSIL, is likely to cause concomitant cervical and vaginal lesions. The accuracy of colposcopy in diagnosing vulvar HSIL is low. Therefore a comprehensive and careful examination of the vulva is necessary and suspicious vulvar lesions should be undergone colposcopy-guided biopsy for diagnosis.

Effect of Alpha Lipoic Acid Supplementation on Oxidative Stress and Lipid Parameters in Women Diagnosed with Low-Grade Squamous Intraepithelial Lesions (LSILs): A Double-Blind, Randomized, Placebo-Controlled Trial.

Limited scientific evidence shows that alpha lipoic acid (ALA) can induce regression rates of low-grade squamous intraepithelial lesions (LSILs), but the mechanisms of these effects have not been elucidated. To gain a broader insight into its therapeutic potential and mechanisms of action, the effects of 3 months of supplementation with 600 mg of ALA on antioxidant and lipid status parameters in 100 patients with LSILs were investigated in a randomized, placebo-controlled study. The obtained results are discussed in terms of patients' initial metabolic status and diet quality (particularly nutritional intake of antioxidants). The obtained results showed that oxidative status biomarkers were not significantly affected by ALA supplementation. However, serum superoxide dismutase (SOD) activity was positively affected in the subgroup of patients with higher dietary antioxidant intake. Surprisingly, ALA supplementation resulted in a small but statistically significant increase in serum low density lipoprotein (LDL), and the observed effect was significantly affected by the initial lipid status of the participants. Larger studies are necessary to gain additional insights on the clinical significance of ALA as an antioxidant and hypolipemic agent and to optimize its potential application in LSIL treatment.

Efficiency of CIN2+ Detection by Thyrotropin-Releasing Hormone (TRH) Site-Specific Methylation.

Cervical cancer screening typically involves a Pap smear combined with high-risk human papillomavirus (hr-HPV) detection. Women with hr-HPV positivity but normal cytology, as well as those with precancerous abnormal cytology, such as low-grade squamous intraepithelial lesions (LSIL) and high-grade SIL (HSIL), are referred for colposcopy and histology examination to identify abnormal lesions, such as cervical intraepithelial neoplasia (CIN) and cervical cancer. However, in order to enhance the accuracy of detection, bioinformatics analysis of a microarray database was performed, which identified cg01009664, a methylation marker of the thyrotropin-releasing hormone (TRH). Consequently, a real-time PCR assay was developed to distinguish CIN2+ (CIN2, CIN3, and cervical cancer) from CIN2- (CIN1 and normal cervical epithelia). The real-time PCR assay utilized specific primers targeting methylated cg01009664 sites, whereas an unmethylated reaction was used to check the DNA quality. A cut-off value for the methylated reaction of Ct < 33 was established, resulting in improved precision in identifying CIN2+. In the first cohort group, the assay demonstrated a sensitivity of 93.7% and a specificity of 98.6%. In the cytology samples identified as atypical squamous cells of undetermined significance (ASC-US) and LSIL, the sensitivity and specificity for detecting CIN2+ were 95.0% and 98.9%, respectively. However, when self-collected samples from women with confirmed histology were tested, the sensitivity for CIN2+ detection dropped to 49.15%, while maintaining a specificity of 100%. Notably, the use of clinician-collected samples increased the sensitivity of TRH methylation testing. TRH methylation analysis can effectively identify women who require referral for colposcopy examinations, aiding in the detection of CIN2+.