High-grade Lesions Research Articles

Study on the clinical characteristics, persistent infection capability and viral load of human papillomavirus type 26 single infection

BackgroundHuman papillomavirus (HPV) infection is the main cause of cervical cancer. Different types of HPV have varying carcinogenic capabilities, and viral load is one of the key indicators of pathogenicity. Currently, there is a lack of clinical data on HPV26. This study analyzed the clinical characteristics of patients with HPV26 single infection.MethodsExfoliated cervical cells were collected for HPV genotyping from women who attended gynecological outpatient clinics or physical examinations. The clinical characteristics of HPV26 single infections in both cross-sectional and follow-up studies were examined, and the association of viral load with HPV26 persistent infection and pathogenicity was investigated.ResultsThe HPV26 positive rate among women visiting hospitals for gynecological medical consultation or physical examination was approximately 0.09% (379/435,072). Among the HPV types tested, the detection rate of HPV26 was 0.37% (379/103,608). In the cross-sectional histopathological study of 101 patients with HPV26 single infection, 62.37% (63/101) presented lesion-free. The numbers of patients with cervical intraepithelial neoplasia (CIN) 1, CIN2, and CIN3 were 25, eight, and five, respectively. Cervical cancer was not detected in any patient. 71 patients attended follow-up examinations as well as HPV26 retesting up to two years, during which, 28.57% (6/21) of CIN1 patients have developed into high-grade lesions, and 9.61% (5/52) of lesion-free patients have progressed to CIN stage. The viral load in the CIN group was significantly higher than that in the lesion-free group (p = 0.012). Similarly, the viral load in the persistent infection group was significantly higher than that in the viral-clearance group (p < 0.001).ConclusionsThe pathogenicity of single HPV26 infections is moderate among high-risk types, warranting the inclusion of HPV26 in expanded screening for HPV. High viral load is an important factor in the persistent infection and pathogenicity of HPV26. Viral load is expected to serve as a screening risk factor for persistent infection and disease progression associated with HPV26.

Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study.

Large randomized clinical trials have demonstrated that human papillomavirus (HPV) testing for high-risk types is more effective than cytology in detecting pre-cancerous lesions and preventing cervical cancer. Its use is being implemented in cervical cancer screening in several countries. The most recent guidelines recommend a risk-based management. It is therefore important to assess the individual risk of having/developing high-grade lesions of women testing high-risk HPV-positive. A crucial viral factor influencing the risk is the HPV genotype since different types are associated to different carcinogenetic risks. Understanding the degree of concordance among different assays targeting either HPV presence/type(s) or cellular morphology and proteins' expression provides knowledge useful to better define how these tests can be used in screening protocols for an effective triage and to anticipate the possible implementation issues. Our study shows that the concordance between tests is higher when the infections have a higher probability of producing a clinically relevant lesion.

The Expression of HPV-16 E5 Oncoprotein Impacts the Transcript Profiles of FGFR2 and EMT-Related Genes in Preneoplastic Anal Epithelium Lesions.

Anal Squamous Cell Carcinoma (SCCA) is a rare Human Papillomavirus type 16 (HPV16)-associated carcinoma whose pathogenesis is still poorly understood. Recent studies based on biopsy and Next Generation Sequencing (NGS) approaches have linked the viral episomal status to aggressive SCCA phenotypes, suggesting a potential role of the 16E5 oncoprotein in tumor development. Our previous findings indicated that 16E5 induces Fibroblast Growth Factor Receptor 2 (FGFR2) isoform switching, aberrant mesenchymal FGFR2c expression, Epithelial Mesenchymal Transition (EMT), and cell invasion in various in vitro human keratinocyte models, as well as in the in vivo context of cervical Low-grade Squamous Intraepithelial Lesions (LSILs). To further explore the role of 16E5 in epithelial carcinogenesis, this study aims to investigate the molecular profile in HPV-related anal lesions. The results showed a significant positive correlation between 16E5 and FGFR2c, as well as 16E5 or FGFR2c and key EMT-related transcription factors, particularly in the group of HPV16 positive anal samples not containing without high grade lesions. Additionally, by coupling the molecular analysis with an interactome investigation, we hypothesized a potential functional interplay between the Ca2+ channel Transient Receptor Potential Ankyrin 1 (TRPA1) and FGFR2c, mediated by 16E5 during the establishment of the oncogenic signaling. These findings will help to elucidate the actual relevance of 16E5 in the early progression of anal lesions and contribute to determine its potential as target for future preventive approaches for HPV16-positive SCCA.

Grade prediction of lesions in cerebral white matter using a convolutional neural network.

We established a diagnostic method for cerebral white matter lesions using MRI images and examined the relationship between the MRI images and the medical checkup data. There were approximately 25 MRI images for each patient's head, from the top of the head to near the eyes. To order these images, we defined the unit of axial for convenience. We varied conditions, such as the location and extent of the images to be loaded, into a convolutional neural network model and verified the changes in discrimination performance on the test data. Co-occurrence network diagrams were also used to determine the relationship between the grade of cerebral white matter lesions and the biochemical test items, which were treated as categorical variables, the progression of cerebral white matter lesions, and patient health status. The convolutional neural network showed the highest discrimination performance when the images were loaded into the model with 80 pixels per side, axial from 9 to 15, along with FLAIR and T1-weighted images. The area under the curve for each grade was 0.9814 for grade 0, 0.9800 for grade 1, 0.9905 for grade 2, 0.9977 for grade 3, and 0.9998 for grade 4. In the co-occurrence network diagram, patients with no or mild cerebral white matter lesions, such as grade 0 and grade 1, had near normal blood pressure, whereas grade 2 patients were closer to (isolated) systolic hypertension. This indicates that patients with higher-grade cerebral white matter lesions tend to experience more severe hypertension.

Cervical cancer screening: efficacy of PAX1 and JAM3 methylation assay in the triage of atypical squamous cell of undetermined significance (ASC-US)

BackgroundAtypical squamous cells of undetermined significance (ASC-US) often present diagnostic challenges with cytology-based results, leading to potential underdiagnosis or overdiagnosis. An effective triage method is essential for managing these cases to reduce unnecessary referrals and treatment.MethodsA total of 322 women diagnosed with ASC-US were tested for HPV-DNA and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test in the study.ResultsMethylation levels of PAX1 and JAM3 were significantly elevated in cervical lesions classified as CIN2 or more severe lesions (CIN2+). The methylation assay demonstrated a sensitivity of 83.8% and a specificity of 95.8%, outperforming HPV-DNA testing in differentiating high-grade cervical lesions among women with ASC-US. Moreover, PAX1m/JAM3m testing significantly reduced the colposcopy referral rate for further diagnostic procedures in high-risk HPV-positive women by 79.5%.ConclusionsPAX1m/JAM3m testing shows promise as a reliable supplemental method to HPV-DNA testing for the triage of women with cytologic ASC-US. In addition, the molecular triage based on the CISCER assay or single PAX1 or JAM3 methylation, had better effects in the women with non-HPV16/18 group. This approach could potentially minimize overtreatment and unnecessary referrals in clinical practice, enhancing patient management and resource utilization.

Prediction of high-grade cervical precancerous abnormalities: The role of personal factors, vaginal microflora, sexually transmitted infections, and high-risk human papillomavirus.

High-risk human papillomavirus infection (HR-HPV) is necessary but not the only factor needed to develop cervical cancer. It is essential to estimate cervical cancer development risk in the population of high-risk HPV-positive women and to avoid unnecessary examinations and treatment in low-risk individuals. The study aimed to identify associations between different personal factors, vaginal microflora, sexually transmitted, high-risk HPV infection, and various degrees of cervical precancerous lesions. A study was performed in 2016-2020. The study group consisted of 112 patients with abnormal cervical cytology results referred for colposcopic examination. 120 women who came for a routine gynecological check-up were included in the control group. Material from the cervix and upper vaginal fornix was taken for pH measurement, wet mount microscopy, testing the six most common high-risk HPV DNA types (16/18, 31, 33, 45, 58), HPV E6/E7 mRNA, and 7 genital infections-C. trachomatis, N. gonorrhea, T. vaginalis, M. hominis, M. genitalium, U. urealyticum, U. parvum. Results showed that women with all grades of cervical intraepithelial neoplasia (CIN) more often were smokers, had increased vaginal pH levels, and had positive HR-HPV DNA and HR HPV E6/E7 mRNA expression. Abnormal vaginal microflora, especially types associated with aerobic vaginitis, and M. hominis were significantly more often found in women with CIN2+. The presence of C.trachomatis, U. parvum, and U.urealyticum did not differ between the groups. The most important factors independently associated with CIN2+ were positive high-risk HPV E6/E7 mRNA expression (OR 59.4, 95% CI 14.84-237.51), and positive high-risk HPV DNA (OR 3.9, 95% CI 1.16-13.23). Higher education level was associated with reduced risk of CIN2+ (OR 0.2, 95% CI 0.07-0.71). In conclusion, this study reports HR-HPV DNA of the most common six types and E6/E7 mRNA positivity as the most significant factors associated with CIN2+ lesions and higher education related to lower risk of high-grade cervical lesions.

Evaluation of endocervical curettage (ECC) in colposcopy for detecting cervical intraepithelial lesions.

Diagnostic challenges in colposcopy arise especially in women aged 50 or older, with postmenopausal status and transformation zone type 3 (TZ3). Endocervical curettage (ECC) is a valuable tool for diagnosing intracervical lesions. The aim of this retrospective analysis was to evaluate the use of ECC in colposcopy for detecting cervical intraepithelial lesions. A retrospective study was carried out of colposcopies performed in the certified Dysplasia Unit at Erlangen University Hospital between July 2016 and June 2023. Pap and human papillomavirus (HPV) results were correlated with the histologic findings via ECC, obtained during examinations or surgery. The primary outcome was the rate of accuracy between the colposcopic and histologic findings with regard to cytology, age of patients, and type of transformation zone (TZ). A total of 429 colposcopies in 413 women with histologic samples obtained via ECC were included in the final analysis. In all, 355 women had TZ3. Among patients with TZ3, evidence of high-grade lesions and invasive carcinoma was also found in women with normal or low-grade abnormal cytology. For patients with normal colposcopic findings, cervical intraepithelial neoplasia (CIN) 2 and CIN3/adenocarcinoma in situ (AIS) were found in 56 patients (16%), and invasive carcinoma was found in four patients (0.1%). This analysis suggests that ECC is a valuable tool in the diagnosis of cervical intraepithelial neoplasia, especially for patients who present with a normal colposcopy of the cervix and vagina but have either recurrent abnormal cytologic findings or high-grade abnormal cytology indicating CIN2 + .

Application of mass cytometry in multiparametric characterization of precancerous cervical lesions.

Cervical cancer (CC) is the fourth most common malignant tumor in women worldwide. Detecting different biomarkers together on single cells by novel method mass cytometry could contribute to more precise screening. Liquid-based cytology (LBC) cervical samples were collected (N = 53) from women categorized as normal and precancerous lesions. Human papillomavirus was genotyped by polymerase chain reaction, while simultaneous examination of the expression of 29 proteins was done by mass cytometry (CyTOF). Differences in cluster abundances were assessed with Spearman's rank correlation as well as high dimensional data analysis (t-SNE, FlowSOM). Cytokeratin (ITGA6, Ck5, Ck10/13, Ck14, Ck7) expression patterns allowed determining the presence of different cells in the cervical epithelium. FlowSOM analysis enabled to phenotype cervical cells in five different metaclusters and find new markers that could be important in CC screening. The markers Ck18, Ck18, and CD63 (Metacluster 3) showed significantly increasing associated with severity of the precancerous lesions (Spearman rank correlation rho 0.304, p = 0.0271), while CD71, KLF4, LRIG1, E-cadherin, Nanog and p53 (Metacluster 1) decreased with severity of the precancerous lesions (Spearman rank correlation rho -0.401, p = 0.0029). Other metaclusters did not show significant correlation, but metacluster 2 (Ck17, MCM, MMP7, CD29, E-cadherin, Nanog, p53) showed higher abundance in low- and high-grade intraepithelial lesion cases. CyTOF appears feasible and should be considered when examining novel biomarkers on cervical LBC samples. This study enabled us to characterize different cells in the cervical epithelium and find markers and populations that could distinguish precancerous lesions.

Post-marketing study design to evaluate the effectiveness of the 9-valent and 4-valent HPV vaccines on serious HPV-related cervical disease in China.

The 4-valent (4 v) and 9-valent (9 v) human papillomavirus (HPV) vaccines are approved in China for females aged 9-45 years. However, the real-world impact of 4vHPV or 9vHPV vaccination for the prevention of high-grade cervical disease in Chinese women is lacking. Two post-marketing surveillance studies will be conducted to measure the occurrence of high-grade cervical lesions in Chinese women who had received ≥1 dose of the 4vHPV (aged 20-45 years) or 9vHPV (aged 16-26 years) vaccine in Ningbo, China. Vaccination data will be extracted from the Ningbo Regional Health Information Platform (NRHIP) from the date of the first 4vHPV (January 9, 2018) or the first 9vHPV (January 25, 2019) vaccination to March 31, 2021. The primary 4vHPV and 9vHPV vaccinated cohorts will include women vaccinated per protocol. The 4vHPV/9vHPV vaccinated test-negative (cervical HPV negative; ThinPrep cytology test negative) and corresponding matched unvaccinated HPV test-negative sub-cohorts will also be assessed. Outcomes will be the occurrence of new-onset cervical intraepithelial neoplasia grade 2/3, adenocarcinoma in situ, and invasive cervical cancer. This study aims to demonstrate that such a methodological approach is feasible and can be used to assess the impact of HPV vaccination in other regions across China.

An integrated approach to secondary prevention of cervical intraepithelial neoplasia

Secondary prevention of cervical precancer is aimed at preventing recurrence of cervical intraepithelial neoplasia (CIN) after excisional treatment. Recurrence of CIN after surgical treatment occurs in 8.1–14.4% of cases, which increases the risk of developing cervical cancer (CC). Despite the high effectiveness of local surgical treatment of patients with high-grade intraepithelial lesions (HSIL), an increased risk of late diagnosis of cervical cancer has been proven in comparison with the risk in the general population. The review article presents current data on factors that increase the potential risk of recurrence of precancer. Human papillomavirus (HPV) persistence is considered one of the leading predictors of relapse of CIN2+, regardless of the type of excision treatment. The combination of persistent high-risk (HR) HPV and a positive sectional margin significantly increases the risk of persistent/recurrent CIN2+. A negative co-test after conization during follow-up contributes to a favorable prognosis and the development of HSIL is observed less frequently than in the population. Only an integrated approach, including detection of cervical HPV HR infection after excisional treatment of CIN, assessment of the radicality of resection and timely measures to eliminate ineffective treatment, as well as subsequent active monitoring of patients, allows avoiding its recurrence and progression of cervical precancer

An unusual liver tumor with challenging morphologic features and immunophenotype: A case report of metastatic HPV-driven basaloid anal squamous cell carcinoma

Abstract Introduction/Objective Basaloid squamous cell carcinoma (BSCC), a rare subtype of squamous cell carcinoma, occurs most commonly in esophagus, lungs, and head and neck. Anal BSCC is extremely rare and has a 10-20% rate of metastasis. High-risk HPV (HR-HPV) is the main causative agent. BSCC occurrence in an atypical site without a known primary tumor, and with atypical immunoprofile can be a diagnostic challenge. Methods/Case Report We report an 83-year-old female with history of breast carcinoma who presented for worsening chest pain. Imaging studies showed pulmonary nodules, 1.8 cm hepatic mass, and pelvic nodules. Liver biopsy showed infiltrating nests of carcinoma with solid and cribriform patterns and luminal necrosis. Some tumor nests had basaloid features with peripheral palisading. Tumor was positive for CK7 and pankeratin; and negative for ER, SOX10, GATA3, GCDFP-15 (Breast markers), CDX2 (GI marker), P63 and P40 (squamous markers), INSM1, Synaptophysin (Neuroendocrine) and TTF1 (lung adenocarcinoma). There was microfocal staining with CK20 and SATB2. Tumor morphology and immunophenotype were not entirely specific to the site of origin. Further search into patient’s medical history showed a recent anal mucosal biopsy revealing a high-grade squamous epithelial lesion with diffuse P16 reactivity. The slides for the anal lesion were reviewed and showed morphologic features similar to the liver biopsy. Additional studies showed both tumors were positive for HR-HPV ISH, P16 (diffuse), and CK5/6 (patchy); and negative for P63. The morphologic features and immunoprofile were supportive of metastasis from HPV-driven BSCC of anus. Subsequent PET Scan revealed a rectal/anal mass. Results (if a Case Study enter NA) NA Conclusion For tumors with unusual morphology and immunophenotype, complete medical history review, and communication with clinician are important tools in achieving correct diagnosis. HR-HPV ISH is a new tool that can be very useful in reaching correct diagnosis in metastatic anogenital or oropharyngeal squamous carcinomas with basaloid features.

Results of Pap Smear in Females Who are Actively Reproducing in Outlying Medical Centers at Parachinar

Objective: To ascertain the prevalence of different cervical abnormalities in connection t pap smear results with age distribution of patient.  Method The demographic makeup of the study population was deduced by calculating the percentages of patients in each age group. Numerous diseases were also identified using the results of the Pap smear test, and percentages associated with each diagnosis were computed. This methodology made it possible to thoroughly analyze the participants' diagnoses and age distribution, which revealed trends in cervical health. One hundred participants in all had Pap smears performed as part of the study. Four age groups were established based on the age distribution data gathered: 18–25, 25–35, 35–45, and 45–55 years old.  Result The majority of participants (37%) were found to be between the ages of 25 and 35, while there was a wide variation of participant ages overall. Pap smear tests are crucial for identifying potentially malignant or precancerous diseases, as evidenced by the majority of patients (71%) receiving a diagnosis of cancer or intraepithelial lesions. There was also representation from the following age groups: 18–25 (9%), 35–45 (28%), and 45–55 (4%). Four percent of the cases had atypical squamous cell lesions, two percent had low-grade squamous intraepithelial lesions, and one percent had high-grade lesions.  Conclusion These findings advance customized screening programs and therapies aimed at specific age groups and diagnostic categories as well as our knowledge of cervical health patterns. People who are fertile should definitely get screened for cervical cancer because the age group of 25 to 35 accounts for a substantial portion of diagnoses. The importance of Pap smear testing for early identification and preventive medicine is underscored by the prevalence of intraepithelial lesions or cancer.

Influence of polymorphisms on the phenotype of TLR1, TLR4 and TLR9 genes and their association with cervical cancer: Bioinformatics prediction analysis and a case-control study

Susceptibility to cervical cancer has been associated with Toll-like receptors (TLRs), which is an important component of innate immunity. According to previous studies, polymorphisms in TLRs genes can affect immune response pathways and lead to the development of cervical cancer. The present study aims to evaluate the functionality of polymorphisms in TLR1, TLR4 and TLR9 genes and their associations with cervical cancer. To identify the functionality of polymorphisms, we used the following tools: MUpro, ChimeraX, SNP2TFBS and GTEx. A case-control study including 57 cases (11 High-grade Intraepithelial Lesion - HSIL and 46 cervical cancer) and 67 clinically healthy controls was conducted in the Brazilian population. Polymorphisms genotyping was performed by real-time PCR, using TaqMan probes, using the allelic discrimination method. Bioinformatics prediction showed that the TLR1 rs4833095 [NM_003263.4 (TLR1):c.743T>C (p.Asn248Ser)] and TLR4 rs4986790 [NM_138554.5 (TLR4):c.896A>G (p.Asp299Gly)] polymorphisms alter the structure and stability of their respective proteins. TLR9 rs187084 [NM_017442.3(TLR9):c.-1486A>G] polymorphism seems to affect the THAP1 binding site and modify gene expression. In the case-control study, the c.743TC heterozygous genotype of the rs4833095 SNP in the TLR1 gene was associated with an increased risk for HSIL/cervical cancer. No association of TLR4 rs4986790 and TLR9 rs187084 SNPs with HSIL/cervical cancer was found in the studied population. Allelic combination CAG (rs4833095/ rs4986790/ rs187084) increased the risk of cervical cancer. In conclusion, the present study identified that polymorphisms in TLRs genes can affect the phenotype of their respective genes and contribute to the development of HSIL or cervical cancer.

Sensitivity, Specificity, and Cost-Benefit Effect Between Primary Human Papillomavirus Testing, Primary Liquid-Based Cytology, and Co-Testing Algorithms for Cervical Lesions.

Cytology has long been a major screening method for cervical cancer prevention. Human papillomavirus (HPV) testing has recently been introduced for cervical cancer screening, and HPV tests become a major screening method in some countries. To seek the optimal strategy considering the cost-effectiveness for cervical cancer screening, we compared the performance of primary LBC, primary HPV test, and LBC plus HPV co-test in real practice. From March 2016 to June 2018, 3742 patients were included in this study. Liquid-based cytology (LBC), HPV test, and histopathological assessment were performed in 3727, 1063, and 508 cases, respectively. The sensitivity, specificity, and cost-benefit effects of primary HPV, primary LBC, and co-test algorithms were simulated for 317 cases with LBC, HPV, and histopathological results. On the LBC, 13.0% of the cases were diagnosed with atypical squamous cells of undetermined significance or higher grade lesions. In the HPV test, high-risk HPV was found in 43.5%, and 11.9% was positive for HPV type 16 or 18. Among the three simulated algorithms, the co-test demonstrated the best sensitivity (97.5%) and the lowest specificity (50.3%). The primary LBC demonstrated the best specificity (53.5%) and a slightly better sensitivity, compare with the primary HPV (95.1% vs. 93.8%). Using the primary LBC algorithm, 82.0% can be determined without additional HPV test, whereas 50.1% could be determined without additional LBC using the primary HPV algorithm. The primary LBC algorithm for uterine cervical cancer (UCC) screening is comparable to the primary HPV algorithm and has the best cost-benefit effect among the three algorithms.

Epidemiological study of human papillomavirus infection in 105,679 women in Wuhan, China

BackgroundQuality assessment of the prevalence and distribution of human papillomavirus (HPV) genotypes could support additional targeted HPV vaccinations. However, the characteristics of HPV infection in Wuhan city are limited in the past decade. We aimed to assess the epidemiology of HPV infection among women and provide a reference for the prevention and treatment of cervical cancer in this region.MethodsA retrospective study employing 105,679 women attending Wuhan Medical and Health Center for Women and Children for cervical cancer screening from January 2015 to December 2022 was conducted. The HPV genotype was detected by polymerase chain reaction (PCR) and diversion hybridization. The overall incidence and age-specific type distribution of HPV infection and the relationship between HPV infection and cervical cytology were analyzed.ResultsThe overall HPV infection rate was 16.87% in Wuhan city, and the prevalence rates of high-risk, low-risk and mixed high- and low-risk HPV infections were 13.64%, 1.77% and 1.46%, respectively. The five most prevalent genotypes were HPV52 (4.24%), HPV58 (2.42%), HPV16 (2.34%), HPV53 (1.87%), and HPV39 (1.66%). The prevalence of HPV in women exhibited a “two-peak” pattern, the peaks of which were observed in the < 21 years group (37.4%) and the 61–65 years group (41.72%). Logistic regression analysis revealed no significant difference in the rate of high-grade lesion positivity between single and multiple high-risk HPV infections. Among patients with a high-grade squamous intraepithelial lesion+ (HSIL+) ThinPrep cytologic test (TCT) diagnosis, HPV58 was the most common type, followed by HPV52, HPV16, HPV39 and HPV53.ConclusionsHPV types 52, 58, 16, 53, and 39 were the most common types in the general female population in Wuhan, and the prevalence of HPV infection varied among different age groups. This study provides a comprehensive overview of the epidemiological characteristics of HPV infection in women, which could support the development of targeted prevention and control strategies for cervical cancer in the region.

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.

Minimally Invasive Direct Coronary Artery Bypass

After experiencing chest pressure while exercising, a 72-year-old patient tested positive in both a stress test and nuclear medicine study, triggering a left heart catheterization that revealed a high grade lesion of the proximal left anterior descending coronary artery. His cardiologist determined the lesion would not be amenable to angioplasty or stenting, so Dr. Marco Zenati performs a minimally invasive coronary artery bypass (MIDCAB).

[Translated article] Retrospective Study of Risk Markers for Developing High-Grade Anal Intraepithelial Neoplasm in Men Who Have Sex With Men Living With HIV

BackgroundHigh-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus (HIV). This condition—the precursor to anal cancer—significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously. Materials and methodsTo describe a population of men who have sex with men living with HIV followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study. ResultsNinety-four patients were analyzed, with a mean age of 39±9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression. DiscussionIn this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education. ConclusionIn men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions.

Prevalence and Description of High-Grade Intraepithelial Lesions of Cervical Mucosa Cells in a Screening Programme for Cervical Cancer in Isère, France.

This study aims to analyse high-grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020. This study included 305,940 asymptomatic women aged 25-65 years. The eligible population was invited to undergo a screening cervico-uterine-smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix. Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25-29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high-grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC-H) smears. In the study population, the prevalence of LIEHG was high in women under 35 years. Low-grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow-up of LSIL and ASC-US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis.

Skin Biopsies and Diagnostic Outcomes at a Multisite Family Medicine Residency Network.

Physicians other than dermatologists evaluate nearly 60% of all skin diseases, and 22% of these physicians are family physicians. Dermatology education is therefore an important aspect of Family Medicine training. Dermatologic procedural training in Family Medicine residency is not standardized, however, so family physicians graduate with highly variable skills. This study describes the scope and diagnostic outcomes of skin biopsies performed by residents at a multisite Family Medicine residency network in comparison with those performed by attendings at a Family Medicine faculty community practice. We performed a retrospective chart review of patients evaluated at eight Family Medicine residency training sites and one Family Medicine faculty community practice within a regional academic health system between January 2020 and October 2022. Patients with a skin finding who underwent at least one skin biopsy during their visit were included in the study. Among all of the skin findings, the incidence of skin biopsy was 3.6% (258/7104) for residents and 1.8% (175/9917) for attendings (P < 0.001). Family Medicine residents performed fewer shave biopsies (57.8% vs 77.7%, P < 0.001) and more punch biopsies (25.6% vs 11.4%, P < 0.001) compared with attendings. Most biopsies performed by residents and attendings were benign, although residents biopsied significantly more benign (79.1% vs 64.6%, P < 0.001) and malignant lesions (11.2% vs 5.7%, P = 0.049). Attendings biopsied significantly more low-to-moderate-grade dysplastic (22.3% vs 5.0%, P < 0.001) and high-grade atypical lesions (4.0% vs 0.8%, P = 0.034). Family Medicine residents at this residency network receive training in a variety of skin biopsy types. Distinct skin biopsy practices and outcomes between residents and attendings may reflect differences in patient populations, clinical expertise, and dermatology referral patterns.