Squamous Intraepithelial Lesions Research Articles

Analysis of natural regression and influencing factors of HSIL in the cervix of childbearing age patients

Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ2=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ2=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.

Reflectance confocal microscopy as a non-invasive imaging tool in vulvar high-grade squamous intraepithelial lesions and lichen sclerosus: A descriptive morphological study in patients and healthy volunteers.

Incorrect and delayed diagnosis of vulvar high-grade squamous intraepithelial neoplasia (vHSIL) and lichen sclerosus (LS) increases malignant progression risks and negatively impacts prognosis and quality of life. There is a need to improve diagnosis and monitoring. Reflectance confocal microscopy is a non-invasive imaging tool that visualizes skin structures at cellular resolution. The objectives were to explore feasibility and patient acceptability of vulvar RCM imaging and to identify RCM characteristics that are discriminative for vulvar HSIL and LS. This was a prospective, cross-sectional, observational clinical trial in patients with vHSIL and LS compared to healthy volunteers. RCM images and vulvar tissue samples were obtained. Five (5) patients with vHSIL, 10 patients with LS and 10 healthy volunteers were enrolled. In total, 100 image series of vulvar skin were obtained, including lesional and nonlesional sites. The RCM technique was considered acceptable for application by patients and healthy controls. Healthy vulvar skin was characterized by a homogenous, normal honeycomb patterned epidermis and a clear epidermal-dermal junctions. Vulvar HSIL and LS displayed an atypical honeycomb pattern of the epidermis and lymphocytic influx with presence of melanophages. Distinct features specifically observed in LS included the presence of hyalinised vessels and sclerotic areas in the dermis. RCM is a non-invasive imaging technique that is feasible and clinically acceptable to apply on vulvar skin, both in patients with premalignant lesions and healthy controls. Recognition and validation of disease-specific characteristics could make reflectance confocal microscopy a clinical tool to non-invasively aid identification of vulvar premalignancies.

Clinical impact of age‑specific distribution of combination patterns of cytology and high‑risk HPV status on cervical intraepithelial neoplasia grade 2 or more.

To the best of our knowledge, the present study is the first to elucidate the significance of cytology and high-risk human papillomavirus (hrHPV) status in different age groups for the detection of cervical intraepithelial neoplasia (CIN)2, CIN3 and squamous cell carcinoma (SCC). There were 12 combinations based on cytology and hrHPV status [cytology: Atypical squamous cells (ASC) of undetermined significance, low-grade squamous intraepithelial lesion, ASC not excluding high-grade squamous intraepithelial lesion (HSIL) and HSIL; hrHPV status: HPV16/18-positive (16/18+), hrHPV positive for subtypes other than 16/18 (others+) and hrHPV-negative (hrHPV-)]. All patients were categorized into four groups based on age (18-29, 30-39, 40-49 and ≥50 years). For patients with CIN2, CIN3 and SCC (CIN2+) (n=107), the distribution of cytology and hrHPV was investigated in each age group. In addition, for all patients (n=446), the occurrence of CIN2+ in each of the 12 combinations was investigated in each age group. In the 18-29-year age group, the most common combination was HSIL and 16/18+, followed by HSIL and others+, which accounted for 73% of CIN2+ cases. The occurrence of HSIL and 16/18+ decreased with increasing age, and no cases occurred in the 50-year age group. In the 18-29-year age group, all patients with HSIL and 16/18+ were diagnosed with CIN2+. CIN2+ was predominantly detected in patients with HSIL in the 18-29-year age group, as well as hrHPV- and others+. This definite distinction was not observed in any other age group. For CIN2+, the distribution patterns of cytology and hrHPV status combinations varied significantly among different age groups. Accordingly, the clinical impact of the combination of cytological findings and hrHPV status can vary among age groups.

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

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

Cervical Precancerous Lesions and Associated Factors Among Women Screened in Two Hospitals in the City of Douala, Cameroon.

Cervical cancer remains the second leading cause of death amongwomen in Cameroon despite the new strategies put in place. This study was conducted in order to determine the prevalence of precancerous cervical lesions and its associated factors in Douala (Cameroon). A cross-sectional study was conducted over a period of nine months in two hospitals of the city of Douala, Cameroon (Laquintinie Hospital and Gyneco-Ostetric and Pediatric Hospital). Cervico-vaginal and endocervical samples were taken from women attending the above-mentioned hospitals in order to identify and characterize precancerous lesions by cytological examinationand to genotype for human papillomavirus (HPV) using the Abbott RealTime High-Risk (HR) HPVkit. Data of sociodemographic characteristics, clinical history, and knowledge about cervical cancer were collected using a questionnaire. Of the 196 women included in this study, 17% had precancerous lesions, including 1.53% for atypical glandular cells (AGC), 4.53% for atypical squamous cells (ASC), 4.53% for low-grade squamous intraepithelial lesion (LSIL), 5.61% for high-grade squamous intraepithelial lesion (HSIL), 0.51% for atypical squamous cells of undetermined significance (ASC-US), and 0.51% for atypical squamous cellscannot exclude HSIL (ASC-H). In addition, the prevalence of HPV infection was 18%, of which 2% was for HPV 16, 2% for HPV 18, and 14% for undetermined HPV. A positive association was recorded between the occurrence of precancerous lesions and HPV infection (P=0.01), age, and school level. Moreover, the occurrence of precancerous lesions was positively associated with the participants' level of knowledge (P=0.01). Precancerous lesions were predominantly HSIL, and the factor most associated with these lesions was HPV infection. This study demonstrates that diagnosis is made at a relatively late stage due to a low level of knowledge about cervical cancer in the population.

Effect of activated glycyrrhizic acid on epithelial cell lipidome in HPV-associated cervical lesions: A prospective cohort study

Aim. To determine the change of lipid levels in the cervical epithelial cells during the treatment of chronic cervicitis and low-grade squamous intraepithelial lesions (LSIL) with 0.1% activated glycyrrhizic acid.&#x0D; Materials and methods. The prospective cohort study included 40 patients with chronic cervicitis and 40 patients with LSIL. Cytological evaluation of cervical smears was performed according to the Bethesda system (2014). All patients received Epigen Intim Spray for 18 months. Amplification of type-specific DNA fragments of human papillomavirus (HPV) and human DNA (sampling control SC) was done using a kit of reagents to detect, type, and quantitatively determine 21 HPV types by Quantum-21 HPV PCR. Lipid extract of a cervical epithelial scraping taken before and after therapy was analyzed by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Lipids were identified using the Lipid Match R-script and by characteristic MS/MS. Correlation analysis of the lipidome of cervicovaginal fluid and SC was performed using the Spearman test, and the Mann-Whitney test was used to compare lipid levels at the two time points.&#x0D; Results. During the treatment of chronic cervicitis, the levels of CL lipids 16:0_16:1_18:1_18:1, HexCer-NDS d20:0/26:0, PC 16: 0_18: 1 and 16: 0_20:4 were decreasing; during the treatment of LSIL, the levels of ceramides and glucosylceramides were decreasing. Chronic cervicitis is characterized by a positive correlation of SC smear with cardiolipins, glucosylceramides, and epithelial lipids with an ether bond; LSIL showed a negative correlation with phosphatidylcholines and phosphatidylethanolamines with an ether bond.&#x0D; Conclusion. As a result of treatment with activated glycyrrhizic acid, the lipid spectrum of epithelial cells significantly changed, depending on the type of lesion. It is also necessary to consider SC scrapings in further studies of epithelial cell lipidome and the type of HPV-associated lesions that affects the adjustments.

HPV16 E6/E7 -based mRNA vaccine is therapeutic in mice bearing aggressive HPV-positive lesions.

HPV (Human papillomavirus) affects 600,000 people worldwide each year. Almost all cervical cancers are associated with a past HPV infection. In particular, the positivity to the high-risk type HPV16 is detected in most of the invasive cervical cancers. FDA has approved prophylactic vaccines that protect against new HPV16 infections, but do not induce immunity in those patients with established infections or neoplasms. To date, no therapeutic vaccine targeting HPV16-associated lesions has been authorized. We have developed an mRNA-based vaccine against the HPV16 late oncoproteins E6 and E7, which are abundantly and exclusively expressed in high-grade squamous intraepithelial lesions (HSILs), a stage of the cervical disease that precedes the progression to carcinoma. Our in vitro and in vivo studies demonstrated that the translated mRNA is functional and elicits an antigen-specific adaptive immune response. Upon immunization with the vaccine, mice with HPV16+ lesions exhibited tumor growth inhibition, extension of lifespan, and development of a protective immune memory. In light of these results and the remarkable clinical success of mRNA vaccines against SARS-CoV2, we believe that our mRNA-based therapeutic vaccine has the potential to offer a non-invasive treatment alternative to the current standard of care for HPV16+ HSILs.

Significance of concurrent HPV testing with unsatisfactory Papanicolaou test for prediction of follow-up HPV, Papanicolaou test, and biopsy results.

Approximately 1% to 2% of routine cytologic specimens collected for Papanicolaou testing are unsatisfactory for evaluation. The American Society for Colposcopy and Cervical Pathology 2019 guidelines recommend repeat testing within 2 to 4 months of an unsatisfactory Papanicolaou test (UPT) result. We evaluated the utility of follow-up Papanicolaou testing, human papillomavirus (HPV) testing, and biopsy in 258 cases of UPTs. High-risk HPV testing was positive in 17.4% (n = 45) and negative in 82.6% (n = 213) of cases at the time of initial UPT; 8.1% (n = 21) of cases had discordant HPV test results. Similarly, 3.8% (n = 8) of initially HPV-negative cases were reported to be HPV-positive on follow-up; 28.9% (n = 13) of initially HPV-positive cases were reported to be HPV negative on follow-up. In total, 27.1% (n = 70) of cases underwent biopsy. Biopsies with significant findings were present in 40% (n = 12) of HPV-positive cases and 7.5% (n = 3) of HPV-negative cases. Low-grade squamous intraepithelial lesion (LSIL) (low-grade cervical intraepithelial neoplasia [CIN-1]) was the most significant finding in all 3 HPV-negative biopsies; 58.3% (n = 7) of HPV-positive biopsies showed LSIL (CIN-1), 13.3% (n = 4) showed HSIL (high-grade CIN), and 3.3% (n = 1) showed invasive carcinoma. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of concurrent HPV testing at the time of UPT for predicting follow-up HPV test result within 1 year of initial UPT are 80.0%, 94.0%, 71.1%, and 96.2%, respectively. The sensitivity, specificity, PPV, and NPV of initial HPV test results for predicting follow-up Papanicolaou test results are 67.7%, 89.7%, 48.8%, and 95.0%, respectively. Concurrent HPV testing in the setting of UPT can be a sensitive tool for predicting follow-up HPV status and significant findings of squamous intraepithelial lesions on follow-up Papanicolaou tests and biopsy.

The effect of aminolevulinic acid hydrochloride topical powder photodynamic therapy versus nocardia rubra cell wall skeleton and observers group in the treatment of cervical low-grade squamous intraepithelial lesions with human papillomavirus infection: A non-randomized study, controlled pilot study.

There are insufficient studies comparing the efficacy of aminolevulinic acid hydrochloride topical powder (ALA) photodynamic therapy (PDT) against Nocardia rubra cell wall skeleton (Nr-CWS) therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with human papillomavirus (HPV), especially for long-term efficacy. Patients with cervical LSIL and HPV infection were divided into 3 treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4 to 6 months and 12 months after the treatment. Among142 patients, patients received 51 ALA PDT and 41 patients received Nr-CWS. Another 50 patients who refused treatment were included in the Observers group. Four to six months or 12 months after treatment, there was significant difference between 3 groups in the clearance rate of HR-HPV infection and the complete remission (CR) rates of cervical LSIL; the CR rates of cervical LSIL in the ALA PDT group was significantly higher than the Nr-CWS group; but there was no significant difference between 2 groups in the clearance rate of HPV infection. The CR rates of cervical LSIL and the clearance rate of HPV infection in the ALA PDT group was significantly higher than the Observers group; the CR rates of cervical LSIL and the clearance rate of HPV infection in the Nr-CWS group was significantly higher than the Observers group; there was no significant difference in the recurrence rates in ALA PDT and Nr-CWS group after 12 months. Both of ALA PDT and Nr-CWS group had lower recurrence rate than the Observers group. The effect of ALA PDT is similar to Nr-CWS in the clearance rate of HR-HPV infection. Compared to the Nr-CWS group, the CR rates of cervical LSIL were considerably greater in the ALA PDT group. The effect of ALA PDT in the clearance rate of HPV infection and CR rates of cervical LSIL was significantly higher than the follow-up group; Both of ALA PDT and Nr-CWS group had lower recurrence rate than the Observers group. For cervical LSIL with HPV infection, ALA PDT is a very successful therapeutic method that is noninvasive.

Variations in Genes Encoding Human Papillomavirus Binding Receptors and Susceptibility to Cervical Precancer.

Cervical cancer oncogenesis starts with human papillomavirus (HPV) cell entry after binding to host cell surface receptors; however, the mechanism is not fully known. We examined polymorphisms in receptor genes hypothesized to be necessary for HPV cell entry and assessed their associations with clinical progression to precancer. African American women (N = 1,728) from the MACS/WIHS Combined Cohort Study were included. Two case-control study designs were used-cases with histology-based precancer (CIN3+) and controls without; and cases with cytology-based precancer [high-grade squamous intraepithelial lesions (HSIL)] and controls without. SNPs in candidate genes (SDC1, SDC2, SDC3, SDC4, GPC1, GPC2, GPC3, GPC4, GPC5, GPC6, and ITGA6) were genotyped using an Illumina Omni2.5-quad beadchip. Logistic regression was used to assess the associations in all participants and by HPV genotypes, after adjusting for age, human immunodeficiency virus serostatus, CD4 T cells, and three principal components for ancestry. Minor alleles in SNPs rs77122854 (SDC3), rs73971695, rs79336862 (ITGA6), rs57528020, rs201337456, rs11987725 (SDC2), rs115880588, rs115738853, and rs9301825 (GPC5) were associated with increased odds of both CIN3+ and HSIL, whereas, rs35927186 (GPC5) was found to decrease the odds for both outcomes (P value ≤ 0.01). Among those infected with Alpha-9 HPV types, rs722377 (SDC3), rs16860468, rs2356798 (ITGA6), rs11987725 (SDC2), and rs3848051 (GPC5) were associated with increased odds of both precancer outcomes. Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical precancer progression. Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical precancer.

High risk HPV testing for cervical cancer screening in a Puerto Rican population

The Human Papillomavirus (HPV) causes cervical cancer, the fourth most common cause of death in women in the United States (US). Several major screening clinical trials have demonstrated that high risk HPV (HR-HPV) DNA primary screen is more sensitive at determining the risk of cervical intraepithelial neoplasia level 3 or higher (CIN ≥ 3) than cytology alone and is similar to co-testing. In this cross-sectional study, we characterized a Hispanic population of 18,052 women ages 21–70 years with HR-HPV DNA testing and cytology to determine the prevalence of HR-HPV in the population and determine the likelihood of high grade squamous intraepithelial lesion (HSIL). We also compared cytology, HR-HPV DNA testing, and co-testing strategies to determine sensitivity, specificity, positive predictive value, and negative predictive value for HSIL in cervical biopsies. Results show that HR-HPV had a slightly higher sensitivity (94.2% vs 92.3%) compared to cytology for all high-grade disease (CIN2/3).

Cumulative incidence of anal cancer since HIV or AIDS diagnosis in the United States.

Treatment of screen-detected anal high-grade squamous intraepithelial lesions has been shown to effectively reduce the incidence of invasive anal cancer in people with HIV. We provide population-based estimates of cumulative incidence of anal cancer by risk group and age at HIV or AIDS diagnosis. The 0- to 10-year cumulative incidence of anal cancer for men who have sex with men and are younger than 30years of age at HIV diagnosis was 0.17% (95% confidence interval [CI] = 0.13% to 0.20%) compared with 0.04% (95% CI = 0.02% to 0.06%) in other men and 0.03% (95% CI = 0.01% to 0.04%) in women. For men who have sex with men and have a diagnosis of AIDS and are younger than 30years of age, the 0- to 10-year cumulative incidence was 0.35% (95% CI = 0.28% to 0.41%). Among people with HIV, men who have sex with men are at the greatest risk of anal cancer, and those with a diagnosis of AIDS had higher risk than those without AIDS. These estimates may inform recommendations for priority populations that could benefit most from anal cancer screening and treatment.

Does the New National Cervical Screening Programme Guideline Detect Cases of High-Grade Squamous Intraepithelial Lesions That Previously Would Have Been Missed?

The aim of this study was to determine the number of patients undergoing large loop excision of the transformation zone (LLETZ), for biopsy-confirmed high-grade squamous intraepithelial lesions (HSIL), where the original cervical screening test (CST) reported oncogenic human papillomavirus (HPV) and negative liquid-based cytology (LBC). This reflects the number of patients where a LLETZ procedure would not have occurred under the previous guideline. Retrospective observational chart review of all patients (n = 477) who underwent LLETZ procedure in a single tertiary unit over a 36-month period. Prevalence of negative histopathology, positive margins, incidental cervical cancer, and accuracy of HSIL identification at colposcopy were measured. Diagnostic accuracy of HSIL diagnosis from initial colposcopic impression was calculated; factors influencing accuracy were evaluated using multivariable logistic regression analysis. There were no comparators. Of 477 LLETZs, 5.9% (n = 28) were for oncogenic HPV and normal LBC on referral CST. Demographics between the "study" (oncogenic HPV and normal LBC on referral CST) and the "standard" group were similar, except the study group was less likely to be using contraception (25% vs 47%, p = .023). In the study group, initial colposcopic cervical biopsy confirmed HSIL in 91.6% (n = 27) and low-grade squamous intraepithelial lesions in 3.6% (n = 1). Histopathological analysis of LLETZ specimens confirmed HSIL in 20 patients (71.4%) and low-grade squamous intraepithelial lesions in 2 (7.1%). No microinvasion was detected. The renewed National Cervical Screening Programme (NCSP), is detecting more "at risk" patients, predicted to lead to a further reduction in incidence of cervical cancer in adequately screened patients.

The cytological pattern of cervical smears of a series of Saudi women in one gynecologic center.

Cervical intraepithelial neoplasia (CIN) is a type of abnormal cervical epithelial development that can lead to cervical malignancy. Thus, the purpose of this study was to examine the cytological pattern of cervical smears from a group of Saudi women who visited a single gynecologic center. From May 2020 to May 2021, 300 women were referred to the cytopathology laboratory and their cytological materials were collected. Because of gynecologic concerns, the women in the study were referred for Pap smears. As part of the obligatory investigations in conjunction with the clinical assessment, a Pap smear is requested. CIN of various grades was found in 11% of the women. High-grade Squamous Intraepithelial Lesions (HSIL) were the most detected modifications, followed by Atypical Squamous Cells of Undetermined Significance (ASUS) and Low-grade Squamous Intraepithelial Lesions (LSIL), accounting for 36.4%, 33.3%, and 30.3%, respectively. In 23.7% of the women, inflammatory cell infiltrations were found. Infection with Candida Albicans was identified in 2.3% of the women. In 15.8% of the patients, cytological evidence of bacterial infection was found. The prevalence of CIN has been growing in Saudi Arabia in recent years, implying a probable involvement in the spread of HPV. Most CIN cases associated with middle age point to HPV infection at a younger age. There is no link between estrogen and/or progesterone levels and CIN.

Detection of DNA Methylation in Gene Loci ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671 for Diagnosis of Cervical Cancer.

To evaluate the diagnostic value of DNA methylation detection of multiple gene loci in cervical cancer. A total of 61 cases requiring cervical biopsy were selected from the outpatient clinic of Maternal and Child Health Hospital of Hubei Province between January 2018 and December 2019. The patients were divided into four groups based on histopathologic diagnosis: cervical cancer (CC) group, high-grade squamous intraepithelial lesion (HSIL) group, low-grade squamous intraepithelial lesion (LSIL) group, and control group. HPV examination, liquid-based cytology examination, and DNA methylation detection at multiple gene sites were performed. The positive rate of DNA methylation, sensitivity, specificity, area under the curve (AUC), and other efficacy indexes were calculated to evaluate the diagnostic value of DNA methylation detection at multiple gene loci in cervical cancer. The positive rates of DNA methylation in CC, HSIL, LSIL, and control groups were 100%, 88%, 83% and 17%, respectively. The ZNF671 gene had the highest positive rate among the cervical lesion group, with rates of 57%, 76%, and 100% in LSIL, HSIL, and CC groups respectively. The combination of DNA methylation detection at multiple gene loci showed the highest diagnostic efficacy for HSIL and cervical cancer, with AUC value of 0.850 (95% CI:0.746-0.954), a Youden index of 0.654, and a sensitivity and specificity of 85% and 85.4%, respectively. The diagnostic efficacy of the combined detection was significantly higher than that of HPV examination and liquid-based cytology examination (P < 0.05). DNA methylation detection at multiple gene loci is highly effective and diagnostic tool for cervical cancer, and has potential application value in clinical practice.

Microbiome-derived cobalamin and succinyl-CoA as biomarkers for improved screening of anal cancer.

Human papillomavirus can cause preinvasive, high-grade squamous intraepithelial lesions (HSILs) as precursors to cancer in the anogenital area, and the microbiome is suggested to be a contributing factor. Men who have sex with men (MSM) living with human immunodeficiency virus (HIV) have a high risk of anal cancer, but current screening strategies for HSIL detection lack specificity. Here, we investigated the anal microbiome to improve HSIL screening. We enrolled participants living with HIV, divided into a discovery (n = 167) and validation cohort (n = 46), and who were predominantly (93.9%) cisgender MSM undergoing HSIL screening with high-resolution anoscopy and anal biopsies. We identified no microbiome composition signatures associated with HSILs, but elevated levels of microbiome-encoded proteins producing succinyl coenzyme A and cobalamin were significantly associated with HSILs in both cohorts. Measurement of these candidate biomarkers alone in anal cytobrushes outperformed anal cytology as a diagnostic indicator for HSILs, increasing the sensitivity from 91.2% to 96.6%, the specificity from 34.1% to 81.8%, and reclassifying 82% of false-positive results as true negatives. We propose that these two microbiome-derived biomarkers may improve the current strategy of anal cancer screening.

Cross-Attention Based Multi-Resolution Feature Fusion Model for Self-Supervised Cervical OCT Image Classification.

Cervical cancer seriously endangers the health of the female reproductive system and even risks women's life in severe cases. Optical coherence tomography (OCT) is a non-invasive, real-time, high-resolution imaging technology for cervical tissues. However, since the interpretation of cervical OCT images is a knowledge-intensive, time-consuming task, it is tough to acquire a large number of high-quality labeled images quickly, which is a big challenge for supervised learning. In this study, we introduce the vision Transformer (ViT) architecture, which has recently achieved impressive results in natural image analysis, into the classification task of cervical OCT images. Our work aims to develop a computer-aided diagnosis (CADx) approach based on a self-supervised ViT-based model to classify cervical OCT images effectively. We leverage masked autoencoders (MAE) to perform self-supervised pre-training on cervical OCT images, so the proposed classification model has a better transfer learning ability. In the fine-tuning process, the ViT-based classification model extracts multi-scale features from OCT images of different resolutions and fuses them with the cross-attention module. The ten-fold cross-validation results on an OCT image dataset from a multi-center clinical study of 733 patients in China indicate that our model achieved an AUC value of 0.9963 ± 0.0069 with a 95.89 ± 3.30% sensitivity and 98.23 ± 1.36 % specificity, outperforming some state-of-the-art classification models based on Transformers and convolutional neural networks (CNNs) in the binary classification task of detecting high-risk cervical diseases, including high-grade squamous intraepithelial lesion (HSIL) and cervical cancer. Furthermore, our model with the cross-shaped voting strategy achieved a sensitivity of 92.06% and specificity of 95.56% on an external validation dataset containing 288 three-dimensional (3D) OCT volumes from 118 Chinese patients in a different new hospital. This result met or exceeded the average of four medical experts who have used OCT for over one year. In addition to promising classification performance, our model has a remarkable ability to detect and visualize local lesions using the attention map of the standard ViT model, providing good interpretability for gynecologists to locate and diagnose possible cervical diseases.

Sequence analysis of exons 30 and 31 of LAMA3 gene variants and its association with human papillomavirus infection predisposition: no evidence was found.

Human papillomavirus (HPV) is associated with cervical cancer. For the infection to occur, most HPV types depend on interactions with heparan sulfate proteoglycans (HSPGs); however, non-HSPGs receptors are also involved. Laminin 332 is a crucial component of the epidermis's base membrane. It has shown interactions with HPV that suggest its function as a transient viral receptor in the extracellular matrix (ECM). We provide new information about Laminin 332 and HPV by identifying LAMA3 gene allelic variants from exons 30 and 31 and their distribution among women with and without HPV infection. We included 192 cervical cancer scrape samples from two groups of patients, 96 samples from patients with a low-grade squamous intraepithelial lesion (LSIL) and 96 samples from HPV-negative samples without LSIL. Identification of the HPV type was performed using an LCD-Array kit. Exons 30 and 31 of LAMA3 were amplified by PCR and analyzed by Sanger's sequencing. We identified a wide range of HPV types. The most frequent low-risk (lrHPV) HPV types were 6, 42, 44, and 90. For high-risk (hrHPV) HPV were 16, 31, 56, and 66. Only the genetic variant rs1131521 was identified in both groups. However, no significant association was observed between rs1131521 and the study groups. A single silent polymorphism was identified in both groups with similar frequency, whereas no mutations related to increased epithelial friability were identified.

High-grade cervical squamous intraepithelial lesions in female partners of men with high-grade penile squamous intraepithelial lesions: a monocentric retrospective study.

We have conducted the first study to focus on the presence of cervical human papillomavirus (HPV) lesions in the female partners of males with high-grade penile squamous intraepithelial lesions (PHSILs). A histologically confirmed cervical squamous intraepithelial lesion (SIL) in female partners was observed in 81% of cases, with high-grade SIL seen in more than two-thirds of cases and low-grade SIL in a third. It is important to screen females whose male partners have PHSIL, in order to detect a clinical HPV lesion early and treat it, if necessary. Our results indicate that a HPV test and reflex cytology (if the HPV test is positive) are necessary for the female partners of males with PHSIL. If there is an abnormal Pap smear, colposcopy should be performed.

Evaluation of the impacts of photodynamic therapy on the prognosis of patients with hrHPV infection based on BTNL8 expression.

The aim of this study was to evaluate the prognostic value of Butyrophilin-like protein 8 (BTNL8) expression in high-risk HPV (hrHPV) infection treated with photodynamic therapy. A total of 93 patients with hrHPV infection were enrolled as research study subjects, along with 69 healthy women who served as controls. Serum samples were obtained from each participant, and BTNL8 levels were quantified. The patients were divided into high- and low-expression groups (n = 45 and n = 48, respectively), and both groups underwent photodynamic therapy. We recorded the following data: BTNL8 expression pre-treatment and at 3/6 months post-treatment, HPV negative conversion ratio, regression rate of low-grade squamous intraepithelial lesions (LSIL), incidence of adverse reactions, complication rate, serum inflammatory factors, persistence of HPV positivity, LSIL residue or recurrence, and incidence of high-grade cervical intraepithelial lesions (HCIL). Patients with HPV infection exhibited higher BTNL8 expression than healthy individuals. Compared to the low-expression group, the high-expression group showed increased HPV negative conversion ratios, LSIL regression rates, and levels of IL-17 and IL-23. This group also demonstrated decreased total complication rate, HPV positivity persistence, LSIL residue or recurrence, and IL-10 levels. Additionally, there was no significant difference between the two groups in terms of the number of adverse reactions and cases with LSIL residue/recurrence. Serum BTNL8 expression may serve as a valuable tool for early screening and prognosis monitoring of patients with hrHPV infection.