Cervical High-grade Squamous Intraepithelial Lesions Research Articles

Photodynamic therapy compared with loop electrosurgical excision procedure in patients with cervical high-grade squamous intraepithelial lesion

The study aimed to compare the effectiveness between Hiporfin-photodynamic therapy (PDT) and loop electrosurgical excision procedure (LEEP) in treating cervical high-grade squamous intraepithelial lesion (HSIL). We conducted a retrospective analysis of 104 women diagnosed with cervical HSIL at our hospital from April 2019 to July 2023. With 1:1 matched case-control, 52 cases received Hiporfin-PDT and 52 cases underwent LEEP. All PDT-treated cases received Hiporfin (2 mg/kg) I.V. and a diode laser at a wavelength of 630-nm. T-test, Chi-square test, Fisher’s exact test, and Yates’s correction for continuity were conducted for statistical. A P value < 0.05 was considered significant. The complete response (CR) post-PDT at 3rd-6th months,10th-12th months and 24th months was in 98.1% (51/52),100.0% (45/45) and 100.0% (22/22) patients respectively, compared to 98.1% (51/52), 100.0% (46/46) and 100.0% (24/24) patients respectively after LEEP. HPV clearance rates after PDT at 3rd-6th months,10th-12th months and 24th months was 76.9% (40/52), 88.9% (40/45) and 95.5% (21/22) respectively, compared to 69.2% (36/52), 93.5% (43/46) and 95.8% (23/24) respectively after LEEP, with no significant difference between the two groups (P = 0.508, P = 0.687 and P = 1.000, respectively). Postoperative complications in the PDT group were tolerable. The cure rates and HPV eradication of Hiporfin-PDT were comparable with that of LEEP in the management of cervical HSIL. Hiporfin-PDT may serve an alternative method for organ-saving in cervical HSIL.

Clinical effect of secondary LEEP combined with transcervical resection of endocervical tissue for cervical precancerous lesions with positive internal margin after the first LEEP

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

Association Between Recurrence of High-grade Squamous Intraepithelial Lesions of the Uterine Cervix and p16, C-myc and PIK3CA Proteins-A Single-center Retrospective Study.

Cervical high-grade squamous intraepithelial lesions (HSIL) are one of the common types of cervical cancer precancerous changes, and HPV16/18 positivity is a risk factor for HSIL recurrence. By detecting the expression of relevant markers in the lesion tissue of recurrent patients, it is helpful for the diagnosis of HPV16/18 positivity and can provide a basis for disease recurrence risk assessment. Therefore, this study analyzed the relationship between p16, C-myc, PIK3CA proteins and HPV16/18 positivity in recurrent cervical HSIL patients. By examining the p16, C-myc, and PIK3CA proteins in the cervical lesion tissue of 180 HSIL recurrent patients who underwent examination in the hospital from January 2020 to December 2022, this study analyzed the relationship between p16, C-myc, and PIK3CA proteins and HPV16/18 positivity. PIK3CA expression detection found that the proportion of positive expression of p16, C-myc, and PIK3CA in HPV16/18 (+) patients was significantly higher than that in HPV16/18 (-), and the expression of HPV16/18 in HSIL patients was significantly positively correlated with p16, C-myc, and PIK3CA. Meanwhile, a prediction model F was constructed based on binary logistic regression analysis data with good fit, and through ROC curve analysis. It was found that p16, C-myc, PIK3CA, and logistic model F can effectively predict HPV16/18 (+), with model F having the best diagnostic performance.

Distribution of 14 High-Risk HPV Types and p16/Ki67 Dual-Stain Status in Post-Colposcopy Histology Results: Negative, Low- and High-Grade Cervical Squamous Intraepithelial Lesions.

Determining the distribution of high-risk human papillomavirus (HR-HPV) types in histologic low-(LSIL) and high-grade (HSIL/CIN2+) squamous intraepithelial lesions through a diagnostic process in a cervical cancer prevention provides one of the key etiological factors behind further progression and persistence. Incorporating novel high-grade cervical lesion biomarkers such as p16/Ki67 dual staining (DS) alongside HPV typing has become important in detecting cervical precancers. Among 28,525 screening tests and 602 histology results, 559 cases with HR-HPV and histology results obtained from colposcopic biopsy were retrospectively analyzed, together with DS status. The χ2 test with Bonferroni correction evaluated the differences in HR-HPV type prevalence and DS positivity across three histologic study groups. A statistically significant difference in the prevalence of HPV 16 was observed between negative and HSIL/CIN2+ (p = 0.00027) groups, as well as between the LSIL/CIN1 and HSIL/CIN2+ groups (p = 0.00041). However, no significant difference was found between the negative and LSIL/CIN1 groups. Similarly, the DS positivity difference was significant between the negative and HSIL/CIN2+ (p < 0.0001) and between the LSIL/CIN1 and HSIL/CIN2+ groups (p < 0.0001), but there was no significant difference between the negative and LSIL/CIN1 groups. The study highlights the heterogeneous nature of HPV-related cervical pathologies, and the distinct risks associated with different cervical lesion grades, emphasizing the importance of HR-HPV type distribution and DS status.

Effect of Clinicopathological Characteristics on the Outcomes of Topical 5-Aminolevulinic Acid Photodynamic Therapy in Patients with Cervical High-Grade Squamous Intraepithelial Lesions (HSIL/CIN2): A Retrospective Cohort Study.

Minimally-invasive 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is used for treating cervical high-grade squamous intraepithelial lesions (HSIL/CIN2). The purpose of this study was to analyze the factors affecting the efficacy of ALA-PDT in the treatment of cervical HSIL/CIN2 in order to guide physicians in making appropriate treatment decisions. A retrospective study including 69 female patients with pathologically diagnosed HSIL/CIN2 was conducted. Patients were given six doses of 20% ALA-PDT at 7-14-day intervals. Cytology, HPV testing, colposcopy, and pathology were performed before treatment and at 6-month follow-up after treatment to assess efficacy. The main outcome of this study was the regression of HSIL/CIN2 and the clearance of high-risk HPV (hrHPV) infection after ALA-PDT treatment. Clinicopathological characteristics were collected to analyze the factors affecting the effectiveness of ALA-PDT treatment for HSIL/CIN2. Between the successful and failed lesion regression group, there was a significant difference in sleeping disorders (p < 0.05). Between the successful and failed hrHPV clearance group, no statistically significant factors were found. With sensitivity values of 0.556 and 0.778, respectively, multivariate analysis showed that current smoking and sleeping disorders were independent prognostics of failure in lesion regression after ALA-PDT treatment. Smoking and sleep disorders were independent risk factors for failure in HSIL/CIN2 regression following ALA-PDT, suggesting the need for careful consideration of ALA-PDT for patients with these conditions.

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.

Unveiling the hidden link: fungi and HPV in cervical lesions.

Cervical cancer, primarily driven by high-risk human papillomavirus (HR-HPV) infection, ranks as the second most common cancer globally. Understanding combined infections' role, including Cervical fungi, is crucial in cervical carcinogenesis. This study aims to explore the potential correlation between HR-HPV, cervical fungi, and cervical cancer, while adjusting for various factors. The study population comprised patients undergoing colposcopy and conization due to abnormal cervical screening results. Clinical data including age, gravidity, HPV (human papillomavirus) genotypes, cervical pathology, and p16/Ki67 expression were extracted. Cervical TCT (ThinPrep Pap Test) and HPV testing are utilized for screening cervical lesions, with fungal presence suggested by TCT results. 5,528 participants were included in this study. Statistical analyses investigated associations between HPV/fungi co-infection and cervical lesions, employing multinomial logistic regression and interaction analysis. Co-infection with fungi and HPV may decrease the risk of cervical lesions compared to HPV infection alone. In the co-infection group, compared with HPV infection alone, the risk of low-grade squamous intraepithelial lesions (LSIL) was reduced by 27% (OR = 0.73, 95% CI: 0.59-0.90), the risk of high-grade squamous intraepithelial lesions (HSIL) was reduced by 35% (OR = 0.65, 95% CI: 0.51-0.82), and the risk of cervical cancer was reduced by 43% (OR = 0.57, 95% CI: 0.35-0.92). The interaction analysis revealed a negative interaction between fungal and HPV infections in the development of cervical cancer (RERI = -6.25, AP = -0.79, SI = 0.52), HSIL (RERI = -19.15, AP = -0.37, SI = 0.72) and LSIL (RERI = -1.87, AP = -0.33, SI = 0.71), suggesting a sub-additive effect, where the combined effect of the two infections was less than the sum of their individual effects. This indicates that fungal infection may attenuate the promoting effect of HPV on cervical lesions. In exploring the potential mechanism, we found that the co-infection group had significantly lower p16 positivity (54.6%) compared to the HPV-only group (60.2%) (p = 0.004), while there was no statistically significant difference in Ki67 positivity. This study unveils the intricate relationship between cervical fungi and HPV in cervical lesions. Co-infection with fungi and HPV against cervical lesions compared to HPV infection alone, indicating a novel clinical interaction. Lower p16 positivity in co-infection hints at a protective mechanism, urging further exploration.

Multiple human papillomavirus infection and high-grade cervical squamous intraepithelial lesions among women with human immunodeficiency virus: a systematic review and a meta-analysis.

This study aimed to evaluate the prevalence of multiple high-risk (HR) human papillomavirus (HPV) infections in women with human immunodeficiency virus (HIV) compared to negative controls. This study also aimed to assess the impact of multiple HR-HPVs on the risk of high-grade squamous cervical lesions (HSILs) among women with HIV. We performed a systematic search of PubMed/Medline, Scopus, Cochrane databases, and ClinicalTrials.gov from 1 January 2004 to 30 June 2023, including screenings and clinical studies evaluating the rates and role of multiple HPV infections in squamous intraepithelial lesions (SILs). Three reviewers independently screened the abstracts of the selected studies and extracted data from full-text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method. Forty-seven studies meet definitive inclusion criteria. The quality of the observations was considered low in 26 of the included studies and moderate in 21 of the included studies. In comparative screening studies, the pooled prevalence of multiple HR-HPV was 39.1% (95% CI = 33.7-44.7) among women with (n = 1734) and 21.6% (95% CI = 17.3-26.1) in those without HIV infection (n = 912) (OR = 2.33, 95% CI = 1.83-2.97, I 2 = 2.8%). The pooled ORs of HR-HPV multiple infections were similar in African (OR = 2.72, 95% CI = 1.89-3.9) and non-African countries (OR = 2.1, 95% CI = 1.46-3, p for difference = 0.96). Among women with HIV, the risk of HSIL diagnosed either by cytology or histology was higher among those with overall (OR = 2.62, 95% CI = 1.62-4.23) and HR multiple infections than those with single HPV infection (OR = 1.93, 95% CI = 1.51-2.46). Among women with HIV, the excess rates of multiple HPV infections and the excess risk of associated HSIL were consistent across studies including both HIV-naïve subjects and those on antiretroviral therapy, as well as in studies with different rates of immunocompromised women. When study quality (low vs. moderate) was used as a moderator, the results were unchanged. Multiple HR-HPV infections are common among women living with HIV and are associated with an increased prevalence of HSIL. These associations were also confirmed in studies with high rates of antiretroviral therapy and low rates of immunocompromise.Systematic Review Registration: PROSPERO [registration number: CRD42023433022].

DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging

Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea.Methylation of EPB41L3 (1–6 CpG-sites), hTERT (1–10 CpG-sites) and FAM19A4 (1–5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously.In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity].Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%.In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.

Cervical dysplasia, cervicitis and inflammatory bowel disease – is there a relationship? (Literature review)

The state of health of the female population of Ukraine is of particular concern due to the year-by-year increase in the frequency of precancerous and oncological diseases of the reproductive organs. Benign and precancerous pathologies of the cervix occupy an important place among gynecological diseases.The objective of this article is to review foreign literature and domestic data sources for assessment the risk of dysplasia and cervical cancer in patients with inflammatory bowel disease (IBD) and cervicitis.Early onset of sexual life and a large number of sexual partners are factors that increase the risk of contracting the human papillomavirus (HPV) and other sexually transmitted infections (STIs). Trauma to the cervical epithelium – mechanical one or caused by an STI – can cause HPV to enter the basal layer of the cervical epithelium. Cervical cancer (CC) is preceded by HPV lesions of the cervical epithelium, including low-grade and high-grade squamous intraepithelial lesions, which are usually diagnosed in women of reproductive age.Cervical intraepithelial neoplasia (CIN) is characterized by impaired maturation and differentiation of cells of the multilayered squamous epithelium and is the most frequent form of morphological precancer of the cervix. Up to 90% of CIN are localized at the border of single-layered cylindrical and multilayered flat epithelium (transformation zone). CIN of various degrees is a precancerous disease in which the index of malignancy (oncological transformation) can reach 50%.The clinical course of dysplastic changes in CIN is asymptomatic, and the patients have no specific complaints. During the infectious process in the vagina, CIN can be accompanied by an increase in the amount of vaginal discharges in the form of mucus or milky secretions. Therefore, in modern conditions timely diagnosis, effective treatment and prevention of precancerous processes, which include CIN of the cervix, is one of the important tasks of a gynecologist. Women of perimenopausal age, who are traditionally classified as a risk group, deserve special attention.Today, there is information in the literature that diseases of a multifactorial nature make up 90–95% of all diseases, which also includes CIN. Despite extensive research efforts and advances in screening and prevention strategies, CC remains an unsolved public health challenge, particularly in low- and middle-income countries. Every year in the world, more than half a million women are diagnosed with CC.The world scientific community pays great attention to the study of epidemiology, pathogenesis, treatment and development of methods of prevention of neoplastic processes in general and CC in particular. So far, this has not been thoroughly studied, and there are no large studies that take into account a variety of potential factors. Understanding the risk factors for the development of CC in patients with IBD and cervicitis may help develop screening and prevention strategies and ultimately improve treatment outcomes.

Identification of exosomal circSLC26A4 as a liquid biopsy marker for cervical cancer.

Circular RNA SLC26A4 (circSLC26A4) functions as an oncogene in the initiation and progression of cervical cancer (CC). However, the clinical role of plasma exosomal circSLC26A4 in CC is poorly known. This study aims to develop an accurate diagnostic method based on circulating exosomal circSLC26A4. In this study, exosomal circSLC26A4 derived from CC cell lines (CaSki, SiHa, and HeLa) and human cervical epithelial cells (HcerEpic) was measured and compared using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Additionally, 56 volunteers, including 18 CC patients, 18 cervical high-grade squamous intraepithelial lesion (HSIL) patients, and 20 healthy volunteers, were enrolled. qRT-PCR was also performed to measure the plasma exosomal circSLC26A4 levels in all participants. The exosomal circSLC26A4 expression level derived from CC cells was significantly elevated compared to it derived from HcerEpic cells. Plasma exosomal circSLC26A4 levels in CC patients were significantly higher than in healthy women and HSIL patients (P < 0.05). In addition, high plasma exosomal circSLC26A4 expression was positively associated with lymph node metastasis and FIGO stage (all P < 0.05). However, no significant correlation was found between plasma exosomal circSLC26A4 expression and age, intravascular cancerous embolus, and perineural invasion (P > 0.05). The high exosomal circSLC26A4 expression is closely related to the occurrence of CC. Plasma exosomal circSLC26A4 can be used as a diagnostic marker for CC.

Development of a machine learning-based model for predicting positive margins in high-grade squamous intraepithelial lesion (HSIL) treatment by Cold Knife Conization(CKC): a single-center retrospective study

ObjectivesThis study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model.MethodWe conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model.ResultsThe overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345–2.189), transformation zone III (OR = 2.838, 95% CI: 2.258–3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247–3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537–2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584–4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593–4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826.ConclusionIndependent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.

Peripheral blood immune cell parameters in patients with high-grade squamous intraepithelial lesion (HSIL) and cervical cancer and their clinical value: a retrospective study

Objective The objective of this study was to delineate the profile of peripheral blood lymphocytic indices in patients afflicted with high-grade squamous intraepithelial lesions (HSIL) and cervical neoplasms, and to elucidate the correlation of these hematologic markers with the clinicopathological spectra in individuals diagnosed with cervical carcinoma. Methods We adopted a retrospective case-control modality for this investigation. An aggregate of 39 HSIL patients and 42 cervical carcinoma patients, who were treated in our facility from July 2020 to September 2023, were meticulously selected. Each case of cervical malignancy was confirmed through rigorous histopathological scrutiny. Concomitantly, 31 healthy female individuals, who underwent prophylactic health evaluations during the corresponding timeframe, were enlisted as the baseline control group. We systematically gathered and analyzed clinical demographics, as well as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), from peripheral blood samples. Pearson’s correlation coefficient was deployed to dissect the interrelation between peripheral NLR and PLR concentrations and the clinicopathological features in the cervical cancer group. Results Inter-group comparative analysis unveiled statistically substantial variances in the PLR and NLR values among the tripartite clusters (F = 36.941, 14.998, P &lt; 0.001, respectively). Although discrepancy in NLR (P = 0.061) and PLR (P = 0.759) measures between the groups of cervical carcinoma and HSIL was not statistically appreciable, these indices were markedly elevated in the cervical carcinoma faction as juxtaposed with the normative control group (t = 5.094, 5.927; P &lt; 0.001 for both parameters). A discernible gradation in peripheral blood PLR and NLR concentrations was noted when stratified by clinical stage and the profundity of myometrial invasion in cervical cancer subjects (P &lt; 0.001). The correlation matrix demonstrated a positive liaison between peripheral blood PLR and the clinical gradation, as well as the invasiveness of the neoplastic cells into the muscularis propria (P &lt; 0.05); a similar trend was observed with the NLR values (P &lt; 0.05). Conclusion Augmented NLR and PLR levels in peripheral blood specimens are indicative of HSIL and cervical malignancy. These hematological parameters exhibit a pronounced interconnection with clinical staging and muscular wall penetration depth, serving as potential discriminative biomarkers for the diagnosis and prognosis of cervical cancer.

Low methylation marker levels among human papillomavirus-vaccinated women with cervical high-grade squamous intraepithelial lesions.

Cervical cancer screening programs, including triage tests, need redesigning as human papillomavirus (HPV)-vaccinated women are entering the programs. Methylation markers offer a potential solution to reduce false-positive rates by identifying clinically relevant cervical lesions with progressive potential. In a nested case-control study, 9242 women who received the three-dose HPV16/18-vaccine at ages 12-15 or 18 in a community-randomized trial were included. Subsequently, they were re-randomized for either frequent or infrequent cervical cancer screening trials. Over a 15-year post-vaccination follow-up until 2022, 17 high-grade squamous intraepithelial lesion (HSIL) and 15 low-grade (LSIL) cases were identified at the 25-year screening round, alongside 371 age and community-matched HPV16/18-vaccinated controls. Methylation analyses were performed on cervical samples collected at age 25, preceding histologically confirmed LSIL or HSIL diagnoses. DNA methylation of viral (HPV16/18/31/33) and host-cell genes (EPB41L3, FAM19A4, and miR124-2) was measured, along with HPV-genotyping. No HPV16/18 HSIL cases were observed. The predominant HPV-genotypes were HPV52 (29.4%), HPV59/HPV51/HPV58 (each 23.5%), and HPV33 (17.7%). Methylation levels were generally low, with no significant differences in mean methylation levels of viral or host-cell genes between the LSIL/HSIL and controls. However, a significant difference in methylation levels was found between HSIL cases and controls when considering a combination of viral genes and EPB41L3 (p value = .0001). HPV-vaccinated women with HSIL had HPV infections with uncommon HPV types that very rarely cause cancer and displayed low methylation levels. Further investigation is warranted to understand the likely regressive nature of HSIL among HPV-vaccinated women and its implications for management.

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.

Clinical analysis of 314 patients with high-grade squamous intraepithelial lesion who underwent total hysterectomy directly: a multi-center, retrospective cohort study

ObjectiveTo identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL.MethodThe clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading.Result1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2–59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244–12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78–23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947–14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892–11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good.ConclusionThere is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

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.

Laminin receptor 1 expression in premalignant and malignant squamous lesions of the cervix

ABSTRACT Laminin receptor 1 (LAMR) may have a role in the progression of premalignant squamous epithelial lesions to cervical cancer. Therefore, we aimed to investigate the expression of laminin receptor 1 (LAMR) in normal, premalignant, and malignant tissues of the uterine cervix. Paraffin blocks of 129 specimens with the diagnoses of normal cervical tissue (n = 33), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2 (n = 14), CIN 3 (n = 28), and squamous cell carcinoma (n = 24) were immunohistochemically stained with LAMR antibody and its expression percentage, pattern, and intensity in these tissues were assessed. Compared to the other groups, the nonstaining with LAMR was highest in low grade squamous intraepithelial lesion (LSIL) (p < 0.0001). LAMR expression, which was positive in less than 50% of cells with weak staining, increased significantly between normal cervical epithelium and high-grade squamous intraepithelial lesion (HSIL) or invasive carcinoma, as well as between LSIL and HSIL (p < 0.0001). Between LSIL and invasive carcinoma, a significant increment was also observed for weak staining in less than 50% of cells (p < 0.001). LAMR expression, which was positive in more than 50% of cells with strong staining, was significantly higher in normal cervical tissue compared to the other groups (p < 0.0001). Disease progression related gradual increment of LAMR expression from normal cervical epithelium or LSIL towards HSIL or cervical cancer reveals that LAMR may play an important role in the transition from premalignant to malignant state in cervical lesions.

The effects of photodynamic therapy on the immune response of women with cervical high-grade squamous intraepithelial lesions

ObjectiveTo evaluate and elucidate the effects and mechanism of photodynamic therapy (PDT) on the immune response of women with cervical high-grade squamous intraepithelial lesions (HSILs). Materials and methodsImmunofluorescence staining was used to compare immune infiltration before and after PDT in 23 patients with cervical HSILs. The infiltration of immune cells into the cervical tissues of patients with different outcomes was also compared at the 6-month follow-up period. Immune cell counts in samples collected before and after treatment were compared. ResultsWe found an increased number of CD8+ T cell infiltration, an increased proportion of CD8+ T cells expressing Granzyme B (GrB), Chemokine receptor 3 (CXCR3), and CD8+ tissue-resident memory T (TRM) cells, and a decreased proportion of CD8+ T cells expressing PD-1 in patients with cervical HSIL compared to that before PDT. Moreover, at the 6-month follow-up, there was higher infiltration of CD8+ T and CD8+ TRM cells, higher expression of GrB and CXCR3, and lower expression of PD-1 on CD8+ T cells in the HPV and cervical HSIL clearance groups than in the persistent HPV infection and cervical HSIL regression groups. However, no significant difference was observed in the number of CD8+ TSCM following PDT. ConclusionPDT activates immune responses mediated by CD8+ T cells. The degree of the immune response is correlated with the prognosis of cervical HSIL.

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.