Bethesda System Research Articles

Application of Machine Learning Algorithms for Risk Stratification and Efficacy Evaluation in Cervical Cancer Screening Among the ASCUS/LSIL Population: Evidence from the Korean HPV Cohort Study.

We assessed human papillomavirus (HPV) genotype-based risk stratification and the efficacy of cytology testing for cervical cancer screening in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL). Between 2010 and 2021, we monitored 1,237 HPV-positive women with ASCUS/LSIL every 6 months for up to 60 months. HPV infections were categorized as persistent (HPV positivity consistently observed post-enrollment), negative (HPV negativity consistently observed post-enrollment), or non-persistent (neither consistently positive nor negative). HPV genotypes were grouped into high-risk (Hr) groups 1 (types 16, 18, 31, 33, 45, 52, and 58) and 2 (types 35, 39, 51, 56, 59, 66, and 68) and a low-risk group. Hr1 was subdivided into types a) 16 and 18; b) 31, 33, and 45; and c) 52 and 58. Cox regression and machine learning (ML) algorithms were used to analyze progression rates. Among 1,273 participants, 17.6% with persistent HPV infections experienced disease progression versus no progression in the HPV-negative group (p<0.001). Cox analysis revealed the highest hazard ratios (HRs) for Hr1-a (11.6, p<0.001), followed by Hr1-b (9.26, p<0.001) and Hr1-c (7.21, p<0.001). HRs peaked at 12-24 months, with Hr1-a maintaining significance at 24-36 months (10.7, p=0.034). ML analysis identified the final cytology change pattern as the most significant factor, with 14-15 months the optimal time for detecting progression from the first examination. In ASCUS/LSIL cases, follow-up strategies should be based on HPV risk types. Annual follow-up was the most effective monitoring for detecting progression/regression.

Directions for Improving the Laboratory Component in Secondary Prevention of Cervical Cancer

Relevance. Effective responses are required due to the high incidence of cervical cancer (Cc) throughout the World. RT-PCRbased HPV-testing is becoming more prominent in secondary prevention worldwide, replacing cytology. Russian practice still relies on cytology as the primary method mainly because there is a lack of comparative evaluation of the diagnostic characteristics of cytology and HPV-tests. Aim. Evaluation of diagnostic characteristics of laboratory methods and the relevance of extended HPV genotyping for secondary prevention of cervical cancer. Materials &amp; methods. The study included data (liquid cytology, histology, HPV-test results) from a survey of 653 women (M = 33.55 years old, ME = 32.0 years old, IQR: 26-38 years old) infected with 14 HPV types (16, 18, 31, 33, 35, 39, 45, 45, 51, 52, 56, 58, 59, 66, 68), with presence or absence of intraepithelial neoplasia of varying severity. The study analyzed the correlation of cervical cytology - histology, clinical sensitivity for high-grade squamous intraepithelial lesions (HSIL+), the incidence and the role of 14 oncogenic HPV types in the development of cervical intraepithelial pathology, positive predictive value (PPV) and the diagnostic accuracy of the HPV-test. Results. The agreement between cytology and histology is 67.20%. Clinical sensitivity of cytology is 83.78% for HSIL+ and 94.34% for any other than NILM result. The structure of the HPV population varies depending on the degree of neoplasia, with a constant predominance of HPV16. The clinical sensitivity of the laboratory component rises to 99.5% by conducting HPV-test for at least 12 types of virus. HSIL is more commonly associated with viruses of alpha-9 phylogenetic group, than with alpha-7 and alpha-5/6. The positive predictive value for HSIL+ is reduced depending on the HPV type: 16&gt;33&gt;58&gt;35&gt;45&gt;31&gt;18&gt;52&gt;39&gt;59&gt;58&gt;56&gt;68&gt;66. Conclusions. Clinical sensitivity of the HPV-test exceeds that of cytology, so that secondary prevention of cervical cancer can be effectively achieved through HPV testing. The introduction of an extended genotyping provides more complete information about the risk of having HSIL+. The data obtained will form the basis for the development of directions for improving the epidemiological surveillance information subsystem of HPVassociated cervical diseases

Optimization of fine-needle aspiration biopsy of the thyroid nodes in complex diagnostic situations

Purpose of the study. To identify the most informative combinations of small non-coding RNA molecules (miRNA) associated with malignant tumors of the thyroid gland (TG) in patients with nodular formations with an uncertain conclusion based on fine needle aspiration biopsy (FNA) and the absence of gene mutations.Materials and methods. The study included 83 patients with thyroid nodules according to the results of ultrasound examination with an indefinite cytological conclusion based on FAB materials (category III–V according to the Bethesda classification) and the absence of V600E mutations in the BRAF gene, NRAS, HRAS, KRAS genes in the molecular genetic study of the aspirate. Expression activity of miRNA was determined by realtime PCR in aspirate. Using cluster analysis, homogeneous groups of miRNAs associated with malignant thyroid lesions in patients were identified.Results. In the cells of thyroid nodules obtained during FNA, malignant lesions are associated with an increase in the expression activity of miRNA‑146b,–221,–222,–885–5p and a decrease in the expression of miRNA‑455–3p and miRNA‑574–3p. Reciprocal changes in expression activity in pairs miRNA‑146b/miRNA‑574–3p, miRNA‑221/miRNA‑455–3p, miRNA‑222/miRNA‑574–3p, miRNA‑885–5p/miRNA‑574–3p are more informative when differential diagnosis of benign and malignant thyroid formations than assessing the expression of individual miRNAs.Conclusion. With an uncertain cytological conclusion based on the FAB data of thyroid nodules (categories III–V according to the Bethesda classification) and negative results of a molecular genetic study regarding gene mutations, it is recommended to direct further diagnostic search in determining the expression in the aspirate of miRNA‑146b,–221,–222,–885–5p,–455–3p,–574–3p.

Characterization of High-Risk-Other Human Papillomavirus Genotypes in Papanicolaou Tests, High-Grade Squamous Intraepithelial Lesions, and Cervical Cancer.

Background: The objective of this study was to determine the human papillomavirus (HPV) genotypes of high-risk-other HPV Papanicolaou (Pap) tests and of biopsy tissues from patients with high-grade squamous intraepithelial lesion (HGSIL) or cervical cancer. High-risk-other HPV status was determined with the cobas HPV Test (Roche Diagnostics, North America) that identifies 12 high-risk, non-16/18 HPV genotypes. We hypothesized that we would find genotypes of HPV in our population that are not covered by the 9-valent HPV vaccine. Methods: For this retrospective cohort study, we randomly selected 50 high-risk-other HPV Pap test samples from 2018 from our pathology department registries for HPV genotype determination by Roche Linear Array (Roche Diagnostics, North America). Then we randomly selected 76 cervical biopsy samples of HGSIL or cervical cancer with high-risk-other HPV or HPV unknown status from 2016 to 2022 for HPV genotype determination by next-generation sequencing. Results are reported as counts and frequencies. Results: In the 50 high-risk-other HPV Pap test samples, 21 genotypes of HPV were noted; the most common were 53 (n=6), 51 (n=6), and 59 (n=5). In the samples with HGSIL or cervical cancer, 16 HPV genotypes were detected; the most common were 16 (n=26), 58 (n=12), and 33 (n=8). Among the patients with HGSIL or cervical cancer, the 9-valent HPV vaccine provided coverage for all the HPV variants found in 88% of patients, partial coverage in 8% of patients, and no coverage in 4% of patients. Conclusion: The 3 most common HPV genotypes seen in our high-risk-other HPV Pap test samples are not covered by the 9-valent HPV vaccine. For the HGSIL and cancer samples, 88% of the samples had full HPV genotype coverage with the 9-valent HPV vaccine. This study highlights a presence of HPV that will not be protected by vaccination in a high-risk population.

Impact of Low-grade Intraepithelial Lesions with High-risk Human Papillomavirus (Part I)

One of the cervical cancer screening tests that has been prevalent in low- and mid-level income countries has been the cytology test, which uses a system of standardized reports such as the Bethesda. This system allows the detection of anomalies in squamous epithelial cells, including the squamous intraepithelial lesion (SIL), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), invasive squamous cell carcinoma, and adenocarcinoma. This categorization in two levels (LSIL and HSIL) has allowed to differentiate the carcinogenic potential of the human papillomavirus (HPV). LSIL are described as transient changes associated with an infection caused by HPV and asymptomatic infections with viral vacuolization within a two-year interval with no specific treatment. In case of HSIL, reference is made to its pre-cancer potential. Several factors have an impact in the onset of a LSIL: the presence of HPV (as one of the key etiologic agents) and other risk factors such as hormones, microbiome, first intercourse at early age, multiple sexual partners, other infections, immune status, and tobaco. All that contribute to the transient nature of the infection, or to its persistence, which in turn may promote the development and progression into an HSIL. The persistence of a high-risk HPV infection (HR-HPV) (or more rarely of low-grade too) plays an important role in the development of cervical cancer.

Diagnostic Performance of Thyroid FNA: Experience of Belarusian National Referral Thyroid Cancer Center.

A fine-needle aspiration (FNA) biopsy is a basic procedure to verify the morphology of thyroid nodules. However, significant variations in the diagnostic performance of FNA, as well as fluctuations in the rate of malignancy (ROM) in different categories of the Bethesda System for Reporting Thyroid Cytopathology, have been discovered in many studies. The development and employment of additional molecular tests in daily clinical practice require an understanding of the prevalence and structure of thyroid malignancy in each category of the Bethesda system. Current research is a continuous retrospective cohort study of the results of the examination and treatment of 1652 patients with thyroid tumors who have undergone primary surgery in 2021 at a national referral thyroid cancer center. FNA diagnostic performance was studied by comparing cytological diagnoses with histological outcomes. The authors evaluated ROM in each Bethesda category and identified the tumors representing a diagnostic pitfall. The overall ROM was 72.4%. When considering ROM in each Bethesda category, it was 16.7% in Bethesda I, 10.1% in Bethesda II, 23.0% in Bethesda IV, 74.8% in Bethesda V, 99.4% in Bethesda VI. The false-positive rate was 65.0%, false negative-0.67%. Follicular and oncocytic adenomas, as well as the follicular variant of papillary thyroid cancer, were the most troublesome entities for patients' management. ROM was comparable to the values implied by the Bethesda system. Follicular tumors were the main source of high false-positive rates. This necessitates the refinement of existing tests and the development of new diagnostic tests to overcome the abovementioned problems.

Analysis of Sensitivity of High Grade Squamous Intraepithelial Lesion (HSIL) Pap diagnosis and Interobserver Variability with Hologic Genius Digital Diagnostics

Analysis of Sensitivity of High Grade Squamous Intraepithelial Lesion (HSIL) Pap diagnosis and Interobserver Variability with Hologic Genius Digital Diagnostics

The Effect of Shared Decision-making on Decision Self-efficacy and Decisional Conflict of Women with Low-grade Squamous Intraepithelial Lesion in Cervical Cytology: An Experimental Study

Background: Women often face decisional challenges and hesitation while choosing the appropriate method to follow up on their abnormal results of cervix cytology. Objective: The present study aimed to determine the effect of shared decision-making (SDM) on decision self-efficacy (DSE) and decisional conflict (DC) about follow-up methods among women with abnormal cervix cytology results. Methods: This interventional study was performed on 54 women referred to the subspecialty clinic of gynecologic oncology. The women were assigned into intervention and control groups using a randomized block design with block sizes of 4 and 6 and an allocation ratio of 1:1. The intervention group received counseling based on the SDM and a decision aid (DA) booklet. The data collection tools included the questionnaires of the demographic and obstetrics characteristics, DC, DSE, and Decision Regret. The collected data were analyzed using SPSS24 software, and independent t-tests and ANCOVA were used. Results: After the intervention, the total mean score of the DC in the intervention group was significantly lower than that in the control group [MD: -22.84 with 95% CI: -23.52 to -21.95, (P &lt;0.001)]. The mean score of DSE in the intervention group was significantly higher than that in the control group [MD: 14.56 with 95% CI: 21.47 to 7.65, (P &lt;0.001)]. Conclusion: The present study results indicated that counseling based on the SDM effectively promotes DSE and reduces DC among women with minor abnormal cervical cytology. Therefore, it is recommended that healthcare providers use SDM for women with abnormal cervical cancer screening results.

An Update on Glacial Acetic Acid Use and Atypical Endocervical and Glandular Cells

An Update on Glacial Acetic Acid Use and Atypical Endocervical and Glandular Cells

A Quality Improvement Study to Evaluate Discordance Rates of Low-Grade Squamous Intraepithelial Lesion on Cervical Pap Smears with Histopathologic Correlation

A Quality Improvement Study to Evaluate Discordance Rates of Low-Grade Squamous Intraepithelial Lesion on Cervical Pap Smears with Histopathologic Correlation

Thyroid Fine Needle Aspiration Cytology with Histologic Correlation and Risk of Malignancy for Bethesda Categories: An Institutional Retrospective Review

Thyroid Fine Needle Aspiration Cytology with Histologic Correlation and Risk of Malignancy for Bethesda Categories: An Institutional Retrospective Review

Molecular Alterations in Suspicious for Follicular Neoplasm (Oncocytic Type) Category of The Bethesda System for Reporting Thyroid Cytopathology

Molecular Alterations in Suspicious for Follicular Neoplasm (Oncocytic Type) Category of The Bethesda System for Reporting Thyroid Cytopathology

Prevalence of malignancy in thyroid nodules with AUS cytopathology: A retrospective cross-sectional study.

Category III (AUS; Atypia of Undetermined Significance) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was established to describe thyroid nodule features that are neither benign nor cancerous. This study aims to evaluate the rate of thyroid malignancy in patients diagnosed with AUS at the Armed Forces Hospital Southern Region (AFHSR), Saudi Arabia. The patients (508) diagnosed with AUS in their thyroid nodules underwent fine-needle aspiration cytology (FNAC). Data were collected through a chart-based approach, reviewing patients' medical records and relevant information. Among the cases, the majority were females (84.6%). Among the different age groups, individuals between 40 and 50 years had the highest prevalence of thyroid nodules (32.5%). Approximately 27% of patients exhibited tumor sizes larger than 4 cm. FNAC results revealed 16.5% benign, 26% AUS, and 22.4% follicular neoplasm cases. Histopathology indicated 54.1% of benign and 37.2% of malignant cases. Papillary carcinoma accounts for 80.4% of all malignant cases. A significant correlation was observed between FNAC and postoperative histopathology (P value < 0.05). Hypoechoic nodules exhibited 33.9% of malignant cases, and calcification was observed in 25% of the cases. A significant association was found between malignancy and echogenicity and between malignancy and calcification (P value = 0.003 and 0.001, respectively). The findings of this study identify malignancy in thyroid nodules with AUS cytopathology, particularly in the Southern region of Saudi Arabia. The correlation between pre-surgery FNAC and postoperative histopathology supports FNAC's diagnostic value. Additionally, echogenicity and calcification can potentially contribute to predicting nodule malignancy.

Pap smear: A preventive approach to screening, diagnosis and management of cervical abnormalities at a tertiary care hospital

Background: Cervical cancer is the second most common cancer among women accounting for 17.7% among all cancers in women. A major contributing factor to the high incidence of the disease in developing countries is due to the lack of efficient screening programmes. The Papanicolaou smear has been well utilized for initial screening of cervical epithelial alterations in order to identify pre-cancerous lesions. Methods: A retrospective observational study was conducted among women who visited gynecological out patient department over 6 months for clinical problem. Pap smear of 600 gynaecology patients of age group 21-60 years were collected. The patients with abnormal epithelial lesions were subjected to cervical punch biopsy. The variables were expressed as frequency and percentages. Results: It was noted that out of the 600 women who had Pap smear screenings, 124 of them had abnormal results. The study participants were divided into two age groups: 43.67% and 30%, respectively, with the 31–40 year old age group coming in first. The majority of them (87.17%) experienced vaginal discharge, and 62.67% reported experiencing abdominal pain. Atypical Squamous Cells of Undetermined Significance (ASCUS) accounted for 38.70% of the epithelial cell abnormalities, followed by Bacterial vaginosis (24.19%) and Trichomonas vaginosis (12.91%). Conclusion: Thus, we draw the conclusion that every woman in the reproductive age group should have a Pap smear test performed because it is an extremely helpful, easy, affordable, and safe method of identifying pre-cancerous cervical epithelial abnormalities.

Cold Knife Conization Vs. Loop Electrosurgical Excision Procedure in Premalignant Cervical Lesions in a Cohort of Females in Romania

Cold knife conization and loop electrosurgical excision procedures (LEEP) are two methods of minimally invasive treatment used in Romania for high-grade cervical dysplasia. The purpose of this study is to identify correlations between the results of the Papanicolaou (PAP) smear and biopsy and to evaluate the positivity of resection margins in both types of conizations: cold knife conization versus LEEP. The 96 cases enrolled in this study were gathered from ‘Prof. Dr. Ioan Pușcaș’ City Hospital of Șimleu Silvaniei, Romania, in a time interval from 01.01.2022 to 01.01.2024. The results of our study showed that out of 20 women who underwent PAP smear for ASC-US, 4 were actually found to have high-grade squamous intraepithelial lesion (H-SIL) according to biopsy results. The estimated risk in females who underwent LEEP procedure with positive margins in the histopathological examination, in the studied population, is almost 0.5 times higher compared to those who underwent cold knife conization. Histopathological examination of cervical specimens is the gold standard method in detecting high-risk cervical lesions. Our study shows that positive deep endocervical margins are more likely to occur in loop electrosurgical excision procedures compared with cold knife conization.

Evaluating the Diagnostic Role of ACR-TIRADS and Bethesda Classifications in Thyroid Nodules Highlighted by Cyto-Histopathological Studies.

To evaluate the accuracy of thyroid imaging reporting and data system (ACR-TIRADS) and the Bethesda system for reporting cytopathology (TBSRCP) classifications for identifying or ruling out thyroid malignancy in relation to the gold standard (post-surgical pathology). This cross-sectional study included 573 patients with single or multiple thyroid nodules. Patients were evaluated using the TIRADS and the TBSRCP classification. The data from a cohort of patients who underwent surgery (77/573, 13.4%) were correlated with post-operative pathology and the relevant clinical features of the patients. Of 573 patients, 545 (95.1%) were euthyroid, 24 (4.1%) were hypothyroid, and 4 (0.8%) were hyperthyroid; 419 (73.1%) had benign nodules (Bethesda II), 115 (20.1%) had intermediate (Bethesda III, IV), and 39 (6.8%) had Bethesda V and VI nodules. Four-hundred twenty (73.3%) patients were categorized as TIRADS 2,3, and 153 (26.7%) were categorized as TIRADS 4,5. The Bethesda and TIRADS classifications concorded significantly in thyroid nodule diagnosis (K=14.9%, P<0.001).Thyroid malignancy was significantly associated with microcalcification and interrupted halo, while benign nodules were significantly associated with macrocalcification and complete halo type (P=0.041, P=0.005, respectively). The TBSRCP could significantly detect malignant thyroid nodules with a sensitivity, specificity, PPV, and NPV of 64.1%, 98.1%, 85.0%, and 94.1%, respectively (K=88.2%, P<0.001), while the respective values for the TIRADS classification were 63.5%, 76.0%, 84.6%, and 50.0% (K=34.8%, P=0.001). The TIRADS and TBSRCP are essential primary steps for evaluating thyroid nodules and both are complimentary. Hence, each patient with thyroid nodules should be evaluated by both approaches before opting for surgery. Highly suspicious TIRADS categories TR4 and TR5 need further evaluation by fine needle aspiration cytology.

Comparative analysis of Paiteling a traditional Chinese medicine (TCM) and CO2 laser therapy for high-risk HPV-associated with LSIL (CIN1) lesions

ObjectivesThis study aims to evaluate the therapeutic outcomes of Paiteling and CO2 laser therapy on high-risk human papillomavirus. MethodsWe retrospectively analyzed the data of 558 patients with HR-HPV low-grade squamous intraepithelial neoplasia (CIN1) from 2021 to 2023. Patients were selected and put into two groups: Paiteling and CO2 laser. Out of the 558 patients who were included in our final study, 239 (42.8 %) were treated with Paiteling, and 319 (57.2 %) were treated with CO2 laser vaporization. The mean age was 49.55 ± 12.10 years old. We observed that 27 (4.83 %) were younger than 30 years and 531 (95.1 %) were older than 30 years. We reviewed the patient’s results at intervals of 3 months, 6 months, 12 months, and 24 months after each therapy. The results of the recurrence rate, effective viral clearance rate, and the effectiveness of both therapies on low-grade cervical lesions were determined using multivariate and univariate cox-regression analysis. The Kaplan-Meier curve was used to determine the HR-HPV conversion rate of each therapy. ResultsThe median time for HR-HPV clearance was 6.00 months (95 % CI: 4.26–6.89) in the Paiteling group and 9.00 months (95 % CI: 15.92–22.67) in the CO2 laser group. There was a significant difference between the two groups (χ2 = 25.118, p-Value = 0.000). The HR-HPV clearance rate during 6–12 months for Paiteling and CO2 laser was 100 (55.6 %) and 80 (44.4 %), respectively. The clearance rate for both therapies from 6 to 18 months was statistically significant (6–12 months: p < 0.010, 12–18 months: p < 0.011). The Paiteling HR-HPV negative rate over 24 months 214 (89.5 %) is higher than CO2 laser 176 (55.2 %). Paiteling has a 5.4 % re-infection rate, which is marginally lower than the 5.6 % rate for CO2 lasers.The clearance rate for both therapies from 12 to 18 months [Paiteling: 20 (4.7 %) to 10 (3.6 %) and CO2 laser: 22 (8.4 %) to 15 (4.2 %)] was also significant (p < 0.011). The percentage of persistent Hr-HPV clearance rate for Paiteling patients was higher than carbon dioxide laser vaporization. No severe side effects were reported by the Paiteling patients compared to laser vaporization. This is due to the fact that Paiteling, as a traditional Chinese medicine, is a topical, non-invasive medicine, thus preserving the integrity of the cervix. ConclusionsPaiteling is an effective noninvasive therapy that can clear persistent HR-HPV associated with cervical low-grade squamous lesions in a relatively shorter period of time compared to CO2 laser ablation.

CAPZB mRNA is a novel biomarker for cervical high-grade squamous lesions

This study aimed to evaluate the potential of capping protein (actin filament) muscle Z-line subunit β (CAPZB) messenger ribonucleic acid (mRNA) levels as a biomarker for distinguishing low-grade squamous intraepithelial lesions of the cervix (LSIL) from high-grade squamous intraepithelial lesions of the cervix (HSIL). We collected a total of 166 cervical exfoliated cells and divided them into five groups based on histopathological results. Each sample was divided into two portions, one for fluorescence in situ hybridization (FISH) detection and the other for bisulfite sequencing polymerase chain reaction (BSP) detection. We found that FISH detection of CAPZB mRNA mean fluorescence intensity (MFI) and BSP detection of CAPZB deoxyribonucleic acid (DNA) percentage of methylation rate (PMR) performed as biomarkers for distinguishing HSIL from LSIL, with an area under the receiver operating characteristic curve (AUC), sensitivity, specificity and cut-off value of 0.893, 81.25%, 80.39% and 0.616, 0.794, 64.06%, 81.37% and 0.454, respectively. Furthermore, FISH detection of CAPZB mRNA exhibited a greater AUC (0.893) for the detection of HSIL than the CAPZB DNA methylation method (0.794), indicating the CAPZB mRNA levels can be used as a biomarker for assessing cervical lesions.

Automated analysis of scattering-based light sheet microscopy images of anal squamous intraepithelial lesions.

We developed an algorithm for automatically analyzing scattering-based light sheet microscopy (sLSM) images of anal squamous intraepithelial lesions. We developed a method for automatically segmenting sLSM images for nuclei and calculating seven features: nuclear intensity, intensity slope as a function of depth, nuclear-to-nuclear distance, nuclear-to-cytoplasm ratio, cell density, nuclear area, and proportion of pixels corresponding to nuclei. 187 images from 80 anal biopsies were used for feature analysis and classifier development. The automated nuclear segmentation method provided reliable performance with the precision of 0.97 and recall of 0.91 when compared with the manual segmentation. Among the seven features, six showed statistically significant differences between high-grade squamous intraepithelial lesion (HSIL) and non-HSIL (non-dysplastic or low-grade squamous intraepithelial lesion, LSIL). A classifier using linear support vector machine (SVM) achieved promising performance in diagnosing HSIL versus non-HSIL: sensitivity of 90%, specificity of 70%, and area under the curve (AUC) of 0.89 for per-image diagnosis, and sensitivity of 90%, specificity of 80%, and AUC of 0.92 for per-biopsy diagnosis.

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.