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Objectives The characterization of DNA polymerase epsilon (POLE) mutations has transformed the classification of endometrial endometrioid carcinomas (EECs), highlighting the need for efficient identification methods. This study aims to examine the relationship between distinct morphologic features—namely, squamous morules and squamous differentiation (SD), as well as β-catenin expression—and the POLE mutation status in endometrial cancer (EC). Methods Our study included 35 POLE-mutated (POLE mut) EC cases and 395 non-POLE mut EEC cases. Results Notably, we observed no presence of morules in POLE mut cases, while SD was identified in 20% of instances. Conversely, morules and SD were identified in 12.7% and 26.1% of non-POLE mut EC cases, respectively, with morules consistently linked to a POLE wild-type status. The nuclear β-catenin expression is typically absent in tumors with wild-type POLE (wt-POLE) status. Conclusions Our findings suggest that the presence of either morules or nuclear β-catenin expression in EEC could practically rule out the presence of POLE mutations. These morphologic and immunohistochemical features can be used as preliminary screening tools for POLE mutations, offering significant savings in time and resources and potentially enhancing clinical decision-making and patient management strategies. However, further validation in larger, multi-institutional studies is required to fully understand the implications of these findings on clinical practice. [ABSTRACT FROM AUTHOR]

This article examines the continuity of heteropatriarchal discourse within China's population policies, focusing on the transition from the one-child policy to the current three-children initiative, and women's responses to these official narratives. Through the lens of Foucauldian bio-politics, the study explores how discursive practices surrounding family planning policy are manipulated to sustain authoritarian rule, linking it with loyalty to the state and fostering an anti-feminist support base that attributes collective feminist movements to "excessive education." The "optimization" of the family planning policy is analyzed as a discursive construct that conceals dehumanizing policies reducing women to mere reproductive machines, and portraying children solely as future labor force. This paper argues that the digital feminist movement in China is sustained by women's constant engagement with, and resistance against official narratives that co-opt feminism to serve the state's bio-political agenda of managing and controlling the female body. [ABSTRACT FROM AUTHOR]

The limited lifespan of batteries is a challenge in the application of implantable electronic devices. Existing wireless power technologies such as ultrasound, near-infrared light and magnetic fields cannot charge devices implanted in deep tissues, resulting in energy attenuation through tissues and thermal generation. Herein, an ultra-low frequency magnetic energy focusing (ULFMEF) methodology was developed for the highly effective wireless powering of deep-tissue implantable devices. A portable transmitter was used to output the low-frequency magnetic field (<50 Hz), which remotely drives the synchronous rotation of a magnetic core integrated within the pellet-like implantable device, generating an internal rotating magnetic field to induce wireless electricity on the coupled coils of the device. The ULFMEF can achieve energy transfer across thick tissues (up to 20 cm) with excellent transferred power (4–15 mW) and non-heat effects in tissues, which is remarkably superior to existing wireless powering technologies. The ULFMEF is demonstrated to wirelessly power implantable micro-LED devices for optogenetic neuromodulation, and wirelessly charged an implantable battery for programmable electrical stimulation on the sciatic nerve. It also bypassed thick and tough protective shells to power the implanted devices. The ULFMEF thus offers a highly advanced methodology for the generation of wireless powered biodevices. [ABSTRACT FROM AUTHOR]

Background Women with human immunodeficiency virus (WWH) have an elevated risk for human papillomavirus (HPV)-associated anal cancer. Primary anal cancer screening results from this population could inform practice guidelines. Methods In total, 381 WWH with anal cytology screening, high-risk HPV (hrHPV) testing and genital (cervical or vaginal) cotesting within 6 months were identified during 2012–2019. Those with anal cytology of atypical squamous cells of undetermined significance (ASCUS) or worse underwent high-resolution anoscopy and biopsy. Independent predictors of anal hrHPV, HPV16, and histological anal high-grade squamous intraepithelial lesions (aHSIL) were identified using adjusted logistic regression models. Results Prevalence of anal hrHPV, HPV16, and ASCUS or worse cytology was 61%, 13%, and 68%. Histological aHSIL was detected in 42% of WWH with ASCUS or worse anal cytology. Prevalence of genital hrHPV, HPV16, and ASCUS or worse cytology was 30%, 4%, and 28%. Genital hrHPV predicted anal hrHPV (odds ratio [OR], 5.05), while genital HPV16 predicted anal HPV16 (OR, 9.52). Genital hrHPV and anal HPV16 predicted histological aHSIL (ORs, 2.78 and 10.9). Conclusions Anal HPV disease was highly prevalent in this primary screening cohort of WWH. While genital screening results predicted anal disease, rates of isolated anal HPV disease were substantial, supporting universal anal cancer screening for this population. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the second leading cause of cancer-induced death in the world. Cancer-associated fibroblasts (CAFs) released exosomes that contributed to cancer progression. This research was carried out to study the influence of CRC-associated fibroblasts-derived exosomes on the phenotype of CRC cells and the underlying mechanism. CAFs-derived exosomes (CAFs-exo) and normal fibroblasts (NFs)-derived exosomes (NFs-exo) were recognized by transmission electronic microscopy, nanoparticle tracking analysis and western blot analysis. Cell counting kit-8, flow cytometry analysis, colony formation assay, Transwell, qRT-PCR, immunofluorescence, immunohistochemistry staining and xenografts model were carried out to proceed with function studies in vitro and in vivo. The results showed that CAFs-exo induced cell proliferation, migration and invasion, while NFs-exo did not influence the tumor biological properties of CRC cells. Using qRT-PCR, miR-345-5p was observed to be a notably up-regulated miRNA in CAFs-exo compared to NFs-exo. CAFs-exo could mediate the transfer of miR-345-5p to CRC cells, and downregulation of miR-345-5p in CAFs notably reversed the pro-tumoral effect of CAFs-exo on CRC cells. Based on online prediction database, CDKN1A was proved as a direct downstream target of miR-345-5p in CRC cells, which was lowly expressed and negatively associated with miR-345-5p in CRC tumors. Furthermore, miR-345-5p upregulation-mediated tumor biological behaviors were abrogated by exogenous CDKN1A. In CRC cells-beared tumor xenograft, CAFs-exo administration promoted tumor growth and decreased CDKN1A expression, whereas miR-345-5p inhibition reversed these effects. The present study revealed that by interacting with CDKN1A, CAF-derived exosomal miR-345-5p promotes CRC progression and metastasis. [ABSTRACT FROM AUTHOR]

Background: Congenital melanocytic naevi (CMN) are known to be associated with mosaic NRAS or BRAF variants. However, the exact correlations of the allele load of mosaic variants in CMN with phenotypic characteristics have not been determined. Aim: To determine the correlation of variants allele load and different phenotypes of CMN. Methods: A panel of genes in the Ras/Raf/MAPK signalling pathway was selected for sequencing in 110 patients with CMN. Correlations between variant allele load and clinical phenotypes, including anatomical localization, projected adult size of the lesion, satellites, subcutaneous nodules, surface rugosity, colour variation and hypertrichosis, were analysed. Results: In addition to the predominant NRAS p.Q61R/K (61.8%) and BRAF p.V600E variants (10%) in patients, we also detected additional variants of NRAS (p.G13R and p.M72fs), BRAF (p.D22N) and MAP2K1 (p.I107fs, p.F209fs, p.Q354H and p.G91_L92insHDQARRLVGDLEHHKPSG). Furthermore, a higher allele load of NRAS p.Q61R/K was found in the trunk and limbs of CMN. It was also found in CMN with larger size, higher colour variation and more significant hypertrichosis, surface rugosity and asymmetry. Conclusion: We discovered more genetic variants of NRAS, BRAF and MAP2K1 and established a correlation between the allele load of NRAS p.Q61R/K and various phenotypes in CMN. The findings of this study potentially facilitate a more accurate and comprehensive classification of CMN in addition to the phenotypic or pathological characteristics used in clinical practice. [ABSTRACT FROM AUTHOR]

In current research on reversible visible watermarking algorithm, the original visible watermark image plays an important auxiliary role, and some algorithms also entirely depend on it to restore host image without any distortion. Therefore, in order to realize semi-blind reversible visible watermarking algorithm, the conventional reversible watermarking algorithm is used to embed compressed visible watermark image data into non-visible-watermarked region of host image. However, the amount of compressed image data obtained by conventional image compression algorithm is relatively large. Therefore, a method based on vectorization compression for the visible watermark image is proposed in this paper. Firstly, it performs edge detection on visible watermark image to obtain a discrete points set |$\Gamma $| of vector contour curve. Then, the discrete points in |$\Gamma $| are simplified by improved Douglas–Peucker algorithm, after that it obtains compressed vector contour data of visible watermark image. In addition, a reversible visible watermarking algorithm based on convolutional relief and image alpha fusion is proposed, which realizes reversible embedding of visible watermark image and lossless restoration of host image. The experimental results show that the proposed vectorization compression method has more advantages than traditional image compression algorithms, which greatly reduces the storage space of visible watermark image with high fidelity. Additionally, the embedded watermarking image has translucent 3D relief effect, and the fusion of host image and visible watermark image becomes more natural and harmonious. [ABSTRACT FROM AUTHOR]

1. There are significant areas of overlap between the rapidly-developing fields of intellectual property (IP) rights and international investment law. Investor-State dispute settlement (ISDS) is a mechanism for adjudicating IP-related investment disputes and enforcing IP rights. The chapter reviews in detail IP investment-related cases that had been brought by the time of writing (pp. 96-133) to provide an understanding of how investment tribunals treat IP-based investments. [Extracted from the article]

Background: Screening strategies for high-risk human papillomavirus (hrHPV)-associated anal cancer are evolving. Herein, we compare anal cytology to hrHPV DNA testing and 2 novel cytology/hrHPV cotesting algorithms among 3 high-risk populations.Methods: Anal cytology, hrHPV DNA testing, and high-resolution anoscopy (HRA)-guided biopsy results were analyzed from 1837 participants (1504 HIV-infected men who have sex with men (MSM), 155 HIV-uninfected MSM, and 178 HIV-infected women). Performance to detect histological high-grade squamous intraepithelial lesions (HSIL)/cancer was compared between 4 strategies with distinct HRA referral thresholds: cytology (atypical squamous cells of undetermined significance, ASCUS); hrHPV testing (any hrHPV positive); algorithm A (benign cytology/HPV16/18 positive or ASCUS/hrHPV positive); and algorithm B (benign or ASCUS/hrHPV positive).Results: Histological HSIL/cancer was detected in 756 (41%) participants. Cytology had the lowest sensitivity (0.76-0.89) but highest specificity (0.33-0.36) overall and for each subgroup. Algorithm B was the most sensitive strategy overall (0.97) and for MSM (HIV-infected 0.97; HIV-uninfected 1.00). For women, hrHPV testing and both algorithms yielded higher sensitivity than cytology (0.96, 0.98, and 0.96). Specificity was low for all strategies/subgroups (range, 0.16-0.36).Conclusions: Screening algorithms that incorporate cytology and hrHPV testing significantly increased sensitivity but decreased specificity to detect anal precancer/cancer among high-risk populations. [ABSTRACT FROM AUTHOR]

Development of novel catalysts for nitrogen reduction at ambient pressures and temperatures with ultrahigh ammonia (NH3) yield and selectivity is challenging. In this work, an atomic catalyst with separated Pd atoms on graphdiyne (Pd-GDY) was synthesized, which shows fascinating electrocatalytic properties for nitrogen reduction. The catalyst has the highest average NH3 yield of 4.45 ± 0.30 mgNH3 mgPd−1 h−1, almost tens of orders larger than for previously reported catalysts, and 100% reaction selectivity in neutral media. Pd-GDY exhibits almost no decreases in NH3 yield and Faradaic efficiency. Density functional theory calculations show that the reaction pathway prefers to perform at the (Pd, C1, C2) active area because of the strongly coupled (Pd, C1, C2), which elevates the selectivity via enhanced electron transfer. By adjusting the p–d coupling accurately, reduction of self-activated nitrogen is promoted by anchoring atom selection, and side effects are minimized. [ABSTRACT FROM AUTHOR]

Objectives: The Lower Anogenital Squamous Terminology (LAST) recommendations classify human papillomavirus-associated squamous lesions into low- and high-grade squamous intraepithelial lesions (LSILs/HSILs). Our study aimed to assess interobserver agreement among 6 experienced pathologists in assigning 40 anal lesions previously diagnosed as anal intraepithelial neoplasia 2 (AIN 2) to either HSIL or non-HSIL categories.Methods: Agreement based on photomicrographs of H&E alone or H&E plus p16 immunohistochemistry was calculated using κ coefficients.Results: Agreement was fair based on H&E alone (κ = 0.42; 95% confidence interval [CI], 0.34-0.52). Adding p16 improved agreement to moderate (κ = 0.55; 95% CI, 0.54-0.62). On final diagnosis, 21 cases (53%) had unanimous diagnoses, and 19 (47%) were divided. When designating p16 results as positive or negative, agreement was excellent (κ = 0.92; 95% CI, 0.83-0.95). Among variables (staining location, extent, and intensity), staining of the basal/parabasal layers was a consistent feature in cases with consensus for positive results (20/20). Of the 67 H&E diagnoses with conflicting p16 results, participants modified 32 (48%), downgrading 23 HSILs and upgrading 9 non-HSILs.Conclusions: Although p16 increased interobserver agreement, disagreement remained considerable regarding intermediate lesions. p16 expression, particularly if negative, can reduce unwarranted HSIL diagnoses and unnecessary treatment. [ABSTRACT FROM AUTHOR]

Background: Squamous cell carcinoma of the anus (SCCA) incidence is rising in the United States. Study of incidence trends by stage at diagnosis, age-specific and birth cohort patterns, and trends in mortality could provide evidence for a true increase and etiological clues for the increase in incidence.Methods: Using the US Cancer Statistics dataset, we examined trends in SCCA incidence (2001-2015) and mortality (2001-2016) rates. Join-point regression was used to compute annual and average annual percentage change (AAPC). Incidence patterns by 5-year age group and birth cohort were evaluated using incidence rate ratios (IRRs) and age-period-cohort modeling.Results: SCCA incidence increased 2.7% per year (95% confidence interval [CI] = 2.1% to 3.3%), with pronounced increases in age groups 50 years and older. Distant-stage SCCA incidence tripled (AAPC = 8.6%, 95% CI = 5.4% to 12.0%, among men and AAPC = 7.5%, 95% CI = 4.8% to 10.2%, among women) and regional-stage SCCA incidence nearly doubled (AAPC = 4.7% for men and women) in both sexes; the AAPC for localized stage was 1.3% (95% CI = 0.6% to 2.0%) in men and 2.3% (95% CI = 1.8% to 2.8%) in women. Compared with adults born circa 1946, recently born black men (born circa 1986) had a nearly fivefold higher risk (IRR = 4.7, 95% CI = 2.1 to 10.2) of SCCA, and the risk doubled among white men (IRR = 2.0, 95% CI = 1.7 to 2.2) and white women (IRR = 2.1, 95% CI = 1.9 to 2.3) born after circa 1960. Anal cancer mortality rates increased 3.1% per year (95% CI = 2.6% to 3.5%) with statistically significant increases in age groups 50 years and older. SCCA incidence-based mortality increased 1.9% annually (95% CI = 0.5% to 3.4%), with a notable (4.9%, 95% CI = 2.4% to 7.3%, per year) rise in adults ages 60-69 years.Conclusion: The increase in SCCA incidence, particularly advanced-stage disease, and a similar increase in mortality suggest a true increase in the occurrence of SCCA. Future research and improved prevention are urgently needed to mitigate the increasing disease burden. [ABSTRACT FROM AUTHOR]

Background: High-risk human papillomavirus (hrHPV)-induced anal low-grade squamous intraepithelial lesions (LSILs) have the potential to progress to high-grade squamous intraepithelial lesions (HSILs). We investigated whether anal hrHPV infections, particularly types 16 and 18, predict LSIL-to-HSIL progression.Methods: One hundred forty-six human immunodeficiency virus (HIV)-infected and 22 HIV-uninfected patients with anal LSILs underwent cytology, HPV genotyping (16, 18, and pooled 12 hrHPV types), and high-resolution anoscopy-guided biopsy at baseline and surveillance. The associations between the rate of LSIL-to-HSIL progression and HPV types as well as longitudinal HPV-16/18 status were assessed by fitting separate Cox regression models.Results: At baseline, 91% of patients harbored hrHPV: HPV-16/18 (44%) and non-16/18 (86%). Upon follow-up (median, 20 [range, 6-36] months), 41% developed HSIL (84% at the same anatomic location as the initial LSIL and 16% at a different location). Baseline HPV-16/18-positive patients had greater probability of progression than patients with non-16/18 types or negative (67%, 25%, and 7%, respectively; P < .001). Persistent HPV-16/18 conferred the highest probability of progression (70%), followed by intermittent HPV-16/18 positivity (52%). In unadjusted and adjusted analyses, baseline and persistent HPV-16/18 were significantly associated with LSIL-to-HSIL progression.Conclusions: Anal LSIL patients who are positive for hrHPV, especially HPV-16/18, have an increased risk of developing HSIL. Type-specific HPV testing could serve as a risk stratification tool, providing prognostic information. [ABSTRACT FROM AUTHOR]

Accumulation of protein aggregates with age was first described in aged human tissue over 150 years ago and has since been described in virtually every human tissue. Ubiquitin modifications are a canonical marker of insoluble protein aggregates; however, the composition of most age-related inclusions remains relatively unknown. To examine the landscape of age-related protein aggregation in vivo, we performed an antibody-based pulldown of ubiquitinated proteins coupled with metabolic labeling and mass spectrometry on young and old mice on calorie restriction (CR), rapamycin (RP)-supplemented, and control diets. We show increased abundance of many ubiquitinated proteins in old mice and greater retention of preexisting (unlabeled) ubiquitinated proteins relative to their unmodified counterparts-fitting the expected profile of age-increased accumulation of long-lived aggregating proteins. Both CR and RP profoundly affected ubiquitinome composition, half-live, and the insolubility of proteins, consistent with their ability to mobilize these age-associated accumulations. Finally, confocal microscopy confirmed the aggregation of two of the top predicted aggregating proteins, keratins 8/18 and catalase, as well as their attenuation by CR and RP. Stable-isotope labeling is a powerful tool to gain novel insights into proteostasis mechanisms, including protein aggregation, and could be used to identify novel therapeutic targets in aging and protein aggregation diseases. [ABSTRACT FROM AUTHOR]

Background: Anal high-grade squamous intraepithelial lesions (HSILs) are the precursors to anal cancer and frequently persist or recur following electrocautery ablation (EA). Impaired mucosal immunity may facilitate anal carcinogenesis. We characterized the immune microenvironment of anal HSILs in correlation with human immunodeficiency virus (HIV) serostatus and ablation outcomes.Methods: Using immunohistochemistry, mucosa-infiltrating CD4+ and CD8+ lymphocytes were quantified in HSILs and benign mucosa from 70 HIV+ and 45 HIV- patients. Clinicopathological parameters were compared.Results: Anal HSILs harbored more T lymphocytes than benign mucosa regardless of HIV status (P ≤ .03). Total T lymphocyte count and CD8+ subset were significantly higher in HIV+ HSILs versus HIV- HSILs (median cell count, 71 vs 47; 47 vs 22/high power field [HPF]; P < .001), whereas the CD4+ subset was comparable between groups (median, 24 vs. 25; P = .40). Post EA, HSILs persisted in 41% of HIV+ and 19% of HIV- patients (P = .04). Unadjusted analysis showed trends toward EA failures associated with HIV seropositivity (incidence rate ratio [IRR], 2.0; 95% CI, .8-4.9) and increased CD8+ cells (IRR, 2.3; 95% CI, .9-5.3).Conclusions: Human immunodeficiency virus is associated with alterations of the immune microenvironment of anal HSILs manifested by increased local lymphocytic infiltrates, predominately CD8+. Human immunodeficiency virus seropositivity and excess mucosa-infiltrating CD8+ cells may be associated with ablation resistance. [ABSTRACT FROM AUTHOR]

Background. Cervical cancer screening is one of the most effective cancer prevention strategies, but most women in Africa have never been screened. In 2007, the Cameroon Baptist Convention Health Services, a large faith-based health care system in Cameroon, initiated the Women's Health Program (WHP) to address this disparity. The WHP provides fee-for-service cervical cancer screening using visual inspection with acetic acid enhanced by digital cervicography (VIA-DC), prioritizing care for women living with HIV/AIDS. They also provide clinical breast examination, family planning (FP) services, and treatment for reproductive tract infection (RTI). Here, we document the strengths and challenges of the WHP screening program and the unique aspects of the WHP model, including a fee-for-service payment system and the provision of other women's health services. Methods. We retrospectively reviewed WHP medical records from women who presented for cervical cancer screening from 2007-2014. Results. In 8 years, WHP nurses screened 44,979 women for cervical cancer. The number of women screened increased nearly every year. The WHP is sustained primarily on fees-for-service, with external funding totaling about $20,000 annually. In 2014, of 12,191 women screened for cervical cancer, 99% received clinical breast exams, 19% received FP services, and 4.7% received treatment for RTIs. We document successes, challenges, solutions implemented, and recommendations for optimizing this screening model. Conclusion. The WHP's experience using a fee-for-service model for cervical cancer screening demonstrates that in Cameroon VIA-DC is acceptable, feasible, and scalable and can be nearly self-sustaining. Integrating other women's health services enabled women to address additional health care needs. [ABSTRACT FROM AUTHOR]

Objectives: Anorectal cytology (ARC) is a widely used screening tool for anal cancer in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Its diagnostic accuracy needs to be improved, especially for high-grade squamous intraepithelial lesions (HSILs).Methods: Using 100 HIV+ MSM with biopsy-proven anal HSILs, we correlated histologic/cytologic findings.Results: Upon review, HSIL cells were present in 58 cytology samples and absent in 42. Positive samples were higher in cellularity and contained transformation zones ( P  < .05). Cytology was able to predict HSILs in 36%, 48%, 68%, and 78% of patients with one, two, three, and four or more high-grade lesions. HSIL cells were identified in all cytology samples initially reported as HSILs or atypical squamous cells, cannot exclude HSIL and in 34 samples reported as low-grade squamous intraepithelial lesions or less. Notably, among this last category, 15 (44%) were keratinized-type HSILs.Conclusions: Our findings should improve the ARC detection rate for anal HSILs, helping to implement ARC as the primary screening tool for anal cancer. [ABSTRACT FROM AUTHOR]

Objectives: To explore the implications of cervical conization specimens lacking the targeted high-grade squamous intraepithelial lesions (negative cone).Methods: We studied 540 conization procedures: 400 positive cones and 140 negative cones. Clinicopathologic features and 2-year follow-up results were reported.Results: Negative cones comprised 22% of procedures triggered by CIN2 or higher biopsies. Procedures triggered by cytology produced much higher percentages of negative cones (37% high-grade squamous intraepithelial lesion [HSIL], 46% atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion [ASC-H], and 76% low-grade squamous intraepithelial lesion-cannot exclude high-grade squamous intraepithelial lesion [LSIL-H]). Upon reviewing negative excision-triggering biopsy and cytology, we downgraded 24 (24%) CIN2 biopsies, three (14%) HSIL, five (83%) ASC-H, and 12 (92%) LSIL-H. One-third of our negative cones can be attributed to overdiagnosis either on biopsy or cytology. Patients with negative cones were older and had smaller excisions, negative colposcopic findings, and negative/equivocal high-risk human papillomavirus (HR-HPV). Within 2 years, 35 (25%) women with negative cones experienced ASCUS or LSIL. Only one (0.7%) recurred as CIN3, a significantly lower percentage than women with positive cones (13%).Conclusions: We advocate careful review of all excision-triggering biopsy and cytology, especially in cases of LSIL-H. Patients with negative cones should be surveyed with cytology and HR-HPV testing. [ABSTRACT FROM AUTHOR]

Objectives: In 2013, the nomenclature for human papillomavirus (HPV)-related lower anogenital squamous lesions was updated to a two-tiered system: high-grade squamous intraepithelial lesion (HSIL) vs low-grade squamous intraepithelial lesion (LSIL). LSIL represents transient HPV infection (CIN1); HSIL represents true cancer precursors (formerly CIN2/3). P16 immunohistochemistry (IHC) plays a critical role in the implementation of this new terminology. However, difficulties arise both in its judicious use and interpretation. Concerning p16 IHC use in grading cervical HPV-related lesions, we set out to determine pathology trainees' proficiency and interpretive skills with a goal of developing targeted, efficient training. Methods: Twelve pathology residents (PGY 2–5) participated in a survey of 20 cervical biopsies that included five unequivocal CIN1, five unequivocal CIN3, and 10 intermediate lesions (CIN2). We recorded trainees' initial H&E diagnosis (CIN1, CIN3, CIN2 requiring p16), frequency of p16 use, p16 interpretation (positive vs negative), and the final diagnosis (LSIL or HSIL) based on combined H&E and p16. Results: Based on H&E morphology, participants' initial diagnostic accuracy was 98% (59/60) for unequivocal CIN3 lesions, 72% (43/60) for unequivocal CIN1 lesions, and 57% (68/120) for CIN2 lesions. P16 IHC was required for an average of 48% of cases (range 30%-65%). Participants correctly interpreted 91% (42/46) of block-positive p16 patterns, 50% (5/10) of negative patterns, and 40% (28/69) of non-block positive patterns including weak/diffuse, strong/focal, and strong/basal stainings. Based on combined H&E and p16 IHC, participants' final diagnostic accuracy was 86% for HSIL and 72% for LSIL. Conclusion: Pathology trainees are up-to-date regarding current terminology and p16 applications. They are proficient in diagnosing unequivocal high-grade and low-grade lesions based on H&E morphology as well as interpreting block-positive p16 results. However, their skill deficiencies lie in handling morphologically intermediate lesions and interpreting non-block p16 staining patterns. We recommend enhanced training targeting these deficiencies. [ABSTRACT FROM AUTHOR]