Surgical protocols for oral leukoplakia and precancerous lesions across three different anatomic sites.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. MATERIALS AND METHODS: A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. RESULTS: Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. CONCLUSION: There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.

Expanding management strategies for cervical precancerous lesions in resource-limited settings: insights from a training center in a district hospital in Ghana.

BACKGROUND: Cervical cancer continues to disproportionately burden women in low/middle-income countries like Ghana. We examined treatment patterns and histopathological outcomes among women screened using visual inspection with acetic acid (VIA) and/or mobile colposcopy who subsequently underwent thermal ablation, large loop excision of the transformation zone (LLETZ), or cold knife conization at the Cervical Cancer Prevention and Training Centre, Battor. We also assessed the prevalence of cervical intraepithelial neoplasia 2+ (CIN2+) or micro-invasive disease and their associated factors for women who underwent excisional treatments. The treatment choices for cervical precancerous lesions suitable for resource-limited settings have also been described from the perspective of a center that manages a heterogenous population. METHODS: We conducted an analysis of secondary data collected between June 2016 and June 2023 among women with positive findings on VIA or mobile colposcopy who subsequently underwent thermal ablation or large loop excision of the transformation zone (LLETZ). The prevalence of histopathology outcomes, including no dysplasia, CIN1 - 3, and micro-invasive disease, were estimated with 95% confidence intervals (CIs). Factors associated with histopathological findings were modeled using multinomial logistic regression. RESULTS: For the study period, 14 (10.6%) of the total 132 participants underwent cervical lesion treatment at outreach locations, all via thermal ablation. The remaining 118 (89.4%) were treated at the Catholic Hospital, Battor using LLETZ (n = 66, 55.9%), thermal ablation (n = 51, 43.2%), and cold knife conization (n = 1, 0.9%). Among 65 women with histopathology reports, the most frequent histopathological finding was no dysplasia (47.7%; 95% CI, 35.1 - 60.5), followed by CIN2 and CIN3 (20.0%; 95% CI, 11.1 - 31.8 each), CIN1 (7.7%; 95% CI, 2.5 - 17.0) and micro-invasion (4.6%; 95% CI, 1.0 - 12.9). Those with micro-invasive disease were significantly older than those with CIN1, CIN2, and CIN3 (p = 0.036, 0.022, 0.009, respectively), but not significantly older than those who showed no dysplasia (p = 0.088). For each unit increase in age, the likelihood of CIN3 was relatively significantly reduced compared to no dysplasia (crude relative risk ratio [RRR] = 0.93; 95% CI, 0.86 - 0.99). This association was neither observed with the remaining histopathological groups nor for parity and persisted after controlling for parity (adjusted RRR = 0.92; 95% CI, 0.85 - 0.99; p = 0.025). CONCLUSION: This paper largely demonstrates treatment options available to women and practitioners in LMICs. The high combined prevalence of high-grade precancerous lesions and micro-invasive disease underscores the need to increase cervical cancer awareness that would enhance screening attendance and hasten efforts at moving from opportunistic to organized screening in Ghana. This will enhance early cervical lesion detection and treatment, while simultaneously re-evaluating and cutting down on unnecessary treatment.

Discontinuation and non-publication of randomized controlled trials on cervical cancer or precancer.

BACKGROUND: Research waste is a considerable problem in clinical trials, with nonpublication being a significant contributor. We aimed to determine the prevalence of discontinuation and nonpublication of randomized controlled trials (RCTs) on cervical cancer or precancer. METHODS: We searched ClinicalTrials.gov for registered RCTs investigating cervical cancer or precancer that started between January 2000 and December 2020. The primary and secondary outcomes were trial nonpublication and premature discontinuation, respectively. Publication status was determined by systematic searches of peer-reviewed journals using the PubMed and Scopus databases. RESULTS: A total of 113 RCTs met the inclusion criteria. Among the 85 trials completed before December 2020, 44 (51.8%) were prematurely discontinued and 40 (47.1%) were unpublished. A single-center design (61.4% vs. 34.1%, P = .012) and lack of external funding (59.1% vs. 36.6%, P = .038) were significantly associated with trial discontinuation. Large-scale (target sample size >400; 46.7% vs. 17.5%, P = .004) and externally funded trials (66.7% vs. 35.0%, P = .004) were more likely to be published. Multivariate logistic analysis revealed that a large sample size [odd ratio (OR): 4.125, 95% confidence interval (CI): 1.511-11.259, P = .006] and presence of external funding (OR: 3.714, 95% CI: 1.513-9.117, P = .004) were independent positive factors for trial publication. CONCLUSION: A significant proportion of RCTs related to cervical cancer or precancer were discontinued early or remain unpublished, resulting in a waste of research resources.

Vulval squamous cell cancer - does precursor lesion margin status affect recurrence-free survival after optimal surgical resection for early-stage disease?

OBJECTIVES: Vulval cancer accounts for around 4% of all gynaecological malignancies and most tumours ( > 90%) are of a squamous cell histotype. Most lesions arise on a background of differentiated VIN (dVIN) or lichen sclerosus (LS). Surgical treatment has undergone a paradigm shift with less radical surgery being attempted to preserve vulval structure and function, without compromising oncological outcome. MATERIAL AND METHODS: In this single site retrospective analysis, we consider the data from a tertiary oncology unit, to assess progression-free survival based on the presence of a precursor lesion at the margin of resection.123 patients with FIGO stage 1 vulvar SCC (n = 33 1A, n = 90 1B) were included. RESULTS: One Hundred Five patients (85%) had an associated precursor lesion (dVIN and/or LS). Within the follow-up period, 33 patients (26.8%) had invasive recurrence, of which 24 (72.7%) had surgical resection margins which were positive for a precursor lesion. In patients with an acceptable microscopically clear invasive resection margin of > 2 mm the presence of a precursor lesion at the margin conveyed a higher risk of malignant recurrence when compared to those with completely clear margins (HR = 2.42; 95% CI 1.14-5.16). CONCLUSIONS: This study adds to the available literature emphasising the clinical significance of dVIN or LS at the surgical margin of optimally resected disease. In those who have marginal involvement of a precancerous lesion, increased surveillance should be considered. Future work should explore the need for additional adjuvant therapy in this cohort.

Detection of Cervical Precancer Using Visual Inspection Method with Acetic Acid.

BACKGROUND: Cervical cancer screening is the priority activity of the government. Visual inspection with Acetic acid (VIA), Pap smear Liquid-based cytology, and HPV DNA testing are different methods of screening. VIA-based screening is the cost-effective method of screening in a resource-constrained setting like in our country as this doesn't require cyto-histological testing, can be performed by trained paramedics too, and is as accurate as a cytological test. The aim is to explore pre-cancer cervical lesions by screening women in the community by visual inspection using acetic-acid. METHODS: Community-based cross-sectional study done at a health camp setting for three months from March to June 2023. The married non-pregnant women of 30-60 years were screened. Descriptive tests as well as sub-group analysis performed by Chi-Square tests. RESULTS: From ten community health camps, 1255 cases were screened and screen positivity was 14.3%. Positive results were proportionately distributed to all parity by 13-19%. Half of the positive results (47.2%) were in the 34-40 age group. There were no significant differences in screen positivity by parity or vaginal discharge. Menopausal women had 7.7% screen positivity. CONCLUSIONS: The prevalence of VIA positivity in the community was found double the previous facility-based prevalence; and there was no significant difference by parity, menopausal status, and vaginal discharge. The positivity was more in 30-45 years of age.

Men's perceptions and perceived acceptability of their female partner's use of self-administered intravaginal therapies for treatment of cervical precancer in Kenya.

Background: Cervical cancer continues to be a major health issue in low- and middle-income countries (LMICs). Despite increasing access to screening, access to precancer treatment remains a significant challenge in LMICs, highlighting a need for innovative, accessible and resource-appropriate treatment approaches, including self-administered therapies. Methods: A cross-sectional mixed-methods study was conducted among men aged 25-65 with a current female partner in Kisumu County, Kenya. Participants were sequentially recruited and surveyed to evaluate their understanding of human papillomavirus and cervical cancer, their views on screening and treatment and their attitudes toward self-administered therapies. Focus group discussions (FGDs) with a subset of the survey participants further explored their treatment preferences and perceptions. Results: Two hundred fourteen men participated in the survey, and 39 men participated in FGDs. The median age was 39 years, and 51% had a primary school education or less. Most (96%) were in a committed relationship, and 74% earned $10 or less daily. There was strong support for self-administered topical therapies, with 98% willing to support their partners using such treatments if available. Additionally, most participants were open to supporting necessary abstinence or condom use, though 76% believed their partners might hesitate to request condom use. When given an option, most preferred their partner to self-administer such therapies at home compared to provider administration at a health facility, citing convenience, cost-effectiveness and privacy. Preferences varied between two potential therapies, 5-Fluorouracil and Artesunate, based on their administration frequency, duration and abstinence requirements. Qualitative findings largely supported the quantitative analysis. Conclusion: The study demonstrates strong support for self-administered topical therapies for cervical precancer among Kenyan men. Additional research on acceptability, feasibility and efficacy in different LMICs could pave the way for these therapies to help bridge current cervical precancer treatment gaps in these settings.

Safety and adherence to self-administered intravaginal 5-fluorouracil cream following cervical intraepithelial neoplasia (CIN) 2/3 treatment among HIV-positive women in Kenya: A phase 1 clinical trial.

Objective: To determine the safety, tolerance, and adherence to self-administered intravaginal 5% fluorouracil (5FU) cream as adjuvant therapy following cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3) treatment among women living with HIV (WLWH) in Kenya. Methods: A Phase I Pilot trial was performed among 12 WLWH in Kenya, aged 18-49 years between March 2023-February 2024 (ClinicalTrial.gov NCT05362955). Participants self-administered 2g of 5FU intravaginally every other week for eight applications. Safety was assessed using a standardized grading scale, and adherence was evaluated using self-report, inspection of used applicators, and weighing of the study drug. Results: The mean age and CD4 count were 43.9 years and 781 cells/mm3, respectively. Seven (58%) had an 8th-grade education or less. All 12 reported at least one grade I adverse event (AE), 1 (8%) reported a grade 2 AE, no grade 3 or 4 AEs were reported. Increased vaginal discharge (n=9, 75%) and irritation (n=5, 42%), with a mean duration of 3.2 and 2.8 days, respectively, were the most commonly reported AEs. Provider-observed AEs included grade 1 cervical erythema and superficial abrasions. All participants tolerated all eight 5FU doses, and 96% adherence was demonstrated. Conclusion: Self-administered 5FU following CIN2/3 treatment among WLWH in Kisumu, Kenya, was safe, tolerable, and associated with high adherence. Randomized trials are needed to investigate whether adjuvant 5FU can improve treatment outcomes or serve as primary cervical precancer treatment in sub-Saharan Africa. A self-administered therapy may be transformative in increasing access to treatment and, hence, secondary prevention of cervical cancer.

Biomarkers in Cancer Screening: Promises and Challenges in Cancer Early Detection.

Cancer continues to be one the leading causes of death worldwide, primarily due to the late detection of the disease. Cancers detected at early stages may enable more effective intervention of the disease. However, most cancers lack well-established screening procedures except for cancers with an established early asymptomatic phase and clinically validated screening tests. There is a critical need to identify and develop assays/tools in conjunction with imaging approaches for precise screening and detection of the aggressive disease at an early stage. New developments in molecular cancer screening and early detection include germline testing, synthetic biomarkers, and liquid biopsy approaches.

The evolution of lung adenocarcinoma precursors is associated with chromosomal instability and transition from innate to adaptive immune response/evasion.

Studying lung adenocarcinoma (LUAD) early carcinogenesis is challenging, primarily due to the lack of LUAD precursors specimens. We amassed multi-omics data from 213 LUAD and LUAD precursors to identify molecular features underlying LUAD precancer evolution. We observed progressively increasing mutations, chromosomal aberrations, whole genome doubling and genomic instability from precancer to invasive LUAD, indicating aggravating chromosomal instability (CIN). Telomere shortening, a crucial genomic alteration linked to CIN, emerged at precancer stage. Moreover, later-stage lesions demonstrated increasing cancer stemness and decreasing alveolar identity, suggesting epithelial de-differentiation during early LUAD carcinogenesis. The innate immune cells progressively diminished from precancer to invasive LUAD, concomitant with a gradual recruitment of adaptive immune cells (except CD8+ and gamma-delta T cells that decreased in later stages) and upregulation of numerous immune checkpoints, suggesting LUAD precancer evolution is associated with a shift from innate to adaptive immune response and immune evasion mediated by various mechanisms.

"ARVs is for HIV and cream is for HPV or precancer:" Women's Perceptions and Perceived Acceptability of Self-Administered Topical Therapies for Cervical Precancer Treatment: A Qualitative Study from Kenya.

Background: Women in low- and middle-income countries (LMICs) bear a disproportionate burden of global incidence and deaths from cervical cancer, despite being a preventable disease. Prevention efforts in LMICs are hindered in part by lack of access to cervical precancer treatment, due to weak health infrastructure and a lack of adequate human resources to deliver current provider-administered precancer treatments. Innovative strategies are urgently needed to close the cervical precancer treatment gap in LMICs, including the use of self-administered topical therapies for which efficacy evidence is available from high-income settings. We investigated African women's perceptions and perceived acceptability of these therapies for cervical precancer treatment. Methods: Between November 2022 and April 2023, we conducted five focus group discussions (FGDs) with women ages 25-65 years undergoing cervical cancer screening or precancer treatment in Kisumu, Kenya. The FGDs explored women's experiences with screening and precancer treatment, their acceptability of topical therapies for precancer treatment, and perceived barriers and facilitators to uptake. The FGDs were moderated by local qualitative research assistants, conducted in local languages, transcribed, coded, and analyzed using qualitative description using NVIVO software. Results: Twenty-nine women participated, with a mean age of 35.4 years (SD 6.5). All had undergone cervical cancer screening, and 25 (83%) had a history of precancer treatment with ablation or excision. Multiple themes were identified related to women's perceptions of topical therapies. Participants were highly receptive of topical treatments, with many favoring the option of self-administration compared to provider-administration of such therapies. Self-administration of topical therapies was felt to help address challenges associated with current treatment methods, including difficulty in access, pain with procedures, cost, and lack of privacy with pelvic exams. Participants had a preference for topical therapies that are used less frequently compared to those used daily. Conclusions: Among Kenyan women with a history of cervical precancer treatment, self-administered topical therapies for precancer are acceptable and have the potential to address barriers, including access, privacy, and cost, that hinder precancer treatment in LMICs. If supported by efficacy studies in LMICs, self-administered topical therapies offer a scalable approach to closing the precancer treatment gap in LMICs. Trial registration: Not applicable.

HPV DNA Testing and Mobile Colposcopy for Cervical Precancer Screening in HIV Positive Women: A Comparison Between Two Settings in Ghana and Recommendation for Screening.

INTRODUCTION: Women living with HIV (WLHIV) have higher prevalence and persistence rates of high-risk human papillomavirus (hr-HPV) infection with a six-fold increased risk of cervical cancer. Thus, more frequent screening is recommended for WLHIV. OBJECTIVES: This retrospective descriptive cross-sectional study was conducted to investigate and compare the prevalence of hr-HPV infection and abnormal findings on mobile colposcopy in two cohorts of WLHIV following cervical screening in rural and urban settings in Ghana. METHODS: Through the mPharma 10 000 Women Initiative, WLHIV were screened via concurrent hr-HPV DNA testing (MA-6000; Sansure Biotech Inc., Hunan, China) and visual inspection (Enhanced Visual Assessment [EVA] mobile colposcope; MobileODT, Tel Aviv, Israel) by trained nurses. The women were screened while undergoing routine outpatient reviews at HIV clinics held at the Catholic Hospital, Battor (rural setting) and Tema General Hospital (urban setting), both in Ghana. RESULTS: Two-hundred and fifty-eight WLHIV were included in the analysis (rural, n = 132; urban, n = 126). The two groups were comparable in terms of age, time since HIV diagnosis, and duration of treatment for HIV. The hr-HPV prevalence rates were 53.7% (95% CI, 45.3-62.3) and 48.4% (95% CI, 39.7-57.1) among WLHIV screened in the rural vs urban settings (p-value = .388). Abnormal colposcopy findings were found in 8.5% (95% CI, 5.1-11.9) of the WLHIV, with no significant difference in detection rates between the two settings (p-value = .221). Three (13.6%) of 22 women who showed abnormal colposcopic findings underwent loop electrosurgical excision procedure (LEEP), leaving 19/22 women from both rural and urban areas with pending treatment/follow-up results, which demonstrates the difficulty faced in reaching early diagnosis and treatment, regardless of their area of residence. Histopathology following LEEP revealed CIN III in 2 WLHIV (urban setting, both hr-HPV negative) and CIN I in 1 woman in the rural setting (hr-HPV positive). CONCLUSIONS: There is a high prevalence of hr-HPV among WLHIV in both rural and urban settings in this study in Ghana. Concurrent HPV DNA testing with a visual inspection method (colposcopy/VIA) reduces loss to follow-up compared to performing HPV DNA testing as a standalone test and recalling hr-HPV positive women for follow up with a visual inspection method. Concurrent HPV DNA testing and a visual inspection method may also pick up precancerous cervical lesions that are hr-HPV negative and may be missed if HPV DNA testing is performed alone.

Prevalence of high-risk human papillomavirus infection among women with diabetes mellitus in Accra, Ghana.

BACKGROUND: There is increasing evidence of a higher risk and poorer prognosis of cervical cancer among women with diabetes mellitus (DM) compared to the general population. These are mediated by higher susceptibility to persistent high-risk human papillomavirus (hr-HPV) infection due to dysfunctional clearance in an immunocompromised state. We aimed to determine the prevalence of hr-HPV infection and cervical lesions in a cohort of women with DM in Ghana. We further disaggregated the prevalence according to DM type and explored factors associated with hr-HPV infection. METHODS: This retrospective descriptive cross-sectional study assessed 198 women with DM who underwent cervical screening via concurrent hr-HPV DNA testing and visual inspection with acetic acid in an outpatient department of the National Diabetes Management and Research Centre in Korle-Bu Teaching Hospital, Accra from March to May 2022. Univariate and multivariable binary logistic regression were used to explore factors associated with hr-HPV positivity. RESULTS: Among 198 women with DM (mean age, 60.2 ± 12.1 years), the overall hr-HPV prevalence rate was 21.7% (95% CI, 16.1-28.1), disaggregated as 1.5% (95% CI, 0.3-4.4) each for HPV16 and HPV18 and 20.7% (95% CI, 15.3-27.0) for other HPV genotype(s). Respective hr-HPV prevalence rates were 37.5% (95% CI, 15.2-64.6) for type 1 DM, 19.8% (95% CI, 13.9-26.7) for type 2 DM, and 25.0% (95% CI, 8.7-49.1) for unspecified/other DM types. Past use of the combined contraceptive pill independently increased the risk of hr-HPV infection by approximately three times (adjusted odds ratio [aOR] = 2.98; 95% CI, 1.03 - 8.64; p-value = 0.045), whereas each unit increase in FBG level increased the odds of hr-HPV infection by about 15% (aOR = 1.15; 95% CI, 1.02 - 1.30; p-value = 0.021). CONCLUSION: Our study points to a high prevalence of hr-HPV among women with DM and highlights a need for glycemic control among them as this could contribute to lowering their odds of hr-HPV infection. The low overall rates of HPV vaccination and prior screening also indicate a need to build capacity and expand the scope of education and services offered to women with DM as regards cervical precancer screening.

Single-cell Landscape of Malignant Transition: Unraveling Cancer Cell-of-Origin and Heterogeneous Tissue Microenvironment.

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced ANXA1 levels promoted monocyte differentiation toward M1 macrophages and inflammatory responses, whereas during malignant progression, upregulated ANXA1 fostered M2 macrophage polarization and cancer-associated fibroblast transformation by increasing TGF-ß production. Our spatiotemporal analysis further provided insights into mechanisms responsible for immunosuppression and a potential target to control evolution of precancer and mitigate the risk for cancer development.

Perceived acceptability of self-administered topical therapy for cervical precancer treatment among women undergoing cervical cancer screening in Kenya.

Purpose: Innovative strategies are urgently needed to meet the World Health Organization's 2030 target of treating 90% of women with precancerous cervical lesions, especially in countries most affected by cervical cancer. We assessed the acceptability of self-administered intravaginal therapies for treating cervical precancer in women undergoing cervical cancer screening and precancer treatment in Kenya. Methods: We conducted a cross-sectional study among women aged 18 to 65 years undergoing cervical cancer screening or precancer treatment between January and October 2023 in Kisumu County, Kenya. Participants completed a questionnaire about their perceptions and perceived acceptability of self- or provider-administered topical therapies for cervical precancer treatment. Quantitative data were summarized using descriptive statistics. Results: A total of 379 questionnaires were completed. The median age of participants was 35 years (IQR 25-62), 62% had a primary education or less, and 71% earned $5 or less daily. All participants had been screened for cervical cancer, and 191 (51%) had received precancer treatment, primarily thermal ablation. Ninety-eight percent of participants were willing to use a self-administered intravaginal therapy for cervical precancer, if available. The majority, 91%, believed their male partner would support their use. Given a choice, 63% preferred self-admiration at home compared to provider-administration of a topical therapy in the clinic, citing time and cost savings. In multivariate analysis, married women were more likely to expect partner support for self-administration than single women. Participants preferred a therapy used less frequently but for a longer duration, compared to daily use therapy with a shorter duration of use. Conclusions: Self-administered intravaginal therapies for cervical precancer treatment are highly acceptable among women undergoing screening and precancer treatment in Kenya.

Biomarkers in the Diagnosis of Endometrial Precancers. Molecular Characteristics, Candidate Immunohistochemical Markers, and Promising Results of Three-Marker Panel: Current Status and Future Directions.

Endometrial carcinoma stands as the most prevalent gynecological cancer and the fourth most common cancer affecting women. The incidence of endometrial cancer has been steadily increasing over the past decade, posing a significant threat to public health. The early detection of its precancers remains a critical and evolving concern to reduce mortality associated with endometrial carcinoma. In the last decade, our understanding of endometrial carcinoma and its precancers has advanced through systematic investigations into the molecular genetics of endometrial carcinoma and its precancers. In this review, we focus on advances in precancers associated with the endometrioid subtype, by far the most common histologic variant of endometrial adenocarcinoma. Recent investigations have led to the identification of new biomarkers, and the proposed incorporation of these biomarkers or biomarker panels into the diagnostic framework of endometrial carcinoma precancers. Here, we review these recent advances and their relevance to the histopathologic diagnosis of endometrial carcinoma precancers.

"There is nothing that can prevent me from supporting her:" men's perspectives on their involvement and support of women's use of topical therapy for cervical precancer treatment in Kenya.

Purpose: Cervical cancer disproportionately impacts women in low- and middle-income countries (LMICs). The World Health Organization's (WHO) 90/70/90 strategy aims to eliminate cervical cancer by 2030 by increasing HPV vaccination coverage to 90%, screening 70% of eligible women, and effectively treating 90% of those with abnormal results by 2030, potentially preventing 62 million deaths in LMICs. LMICs, however, struggle with limited access to cervical precancer treatment, in part due to a lack of trained professionals and weak health systems. Effective non-surgical, self-administered, which have demonstrated efficacy in high-income countries, could bridge the treatment gap in LMICs and may be more scalable and cost-effective than provider-administered therapies. To inform feasibility studies in LMICs, data are needed on the role of male partners in influencing the acceptability and uptake of self-administered topical therapies, including their support of recommended abstinence and contraception guidelines associated with these therapies. Methods: Between November 2022 and April 2023, we conducted five focus group discussions (FGDs) with men aged 25 to 65 years in Kenya to explore their perspective and perceived support regarding their female partners using topical self-administered therapies for cervical precancer treatment. The FGDs were moderated by local qualitative research assistants and conducted in local languages, transcribed, coded, and analyzed using qualitative description. Results: Thirty-nine male participants meeting the eligibility criteria participated in five FGDs. The mean age of participants was 42.5 years. Most participants, 79.5%, had a female partner with a history of cervical precancer treatment, 5.1% did not, and 15.4% were unsure of their female partner's prior precancer treatment history. The study aimed to assess men's support of their female partners' use of topical therapies for treating cervical precancer. We find that male participants strongly express acceptance and willingness to support their wives or partners in using such therapies, if available. Reported supportive behavior included permitting the use of the therapies and support of maintaining abstinence during the recommended times. Additionally, participants desired male involvement in clinic and community-based education about topical therapies to facilitate widespread support. Conclusion: The use of self-administered topical therapies for cervical precancer treatment, if supported by efficacy studies in LMICs, may support achieving the WHO's 2030 goal of 90% treatment access. We find that with adequate education, men express overwhelming support of their female partner's use of topical therapies, including adherence to abstinence and contraception guidelines.

Biopsy-verified vulvar lichen sclerosus: Incidence trends 1997-2022 and increased risk of vulvar squamous precancer and squamous cell carcinoma.

Population-based data on the epidemiology of vulvar lichen sclerosus (LS) are sparse and only few prospective studies have investigated the malignant potential of the disease. We used the nationwide Danish Pathology Registry to first assess the incidence of biopsy-verified vulvar LS in the period 1997-2022 and second to examine the incidence of vulvar high-grade squamous precancer and squamous cell carcinoma (SCC) in women with biopsy-verified vulvar LS (1978-2019) compared with that expected in the general female population. For the latter aim, we computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). During our study period, the age-standardized incidence rate of vulvar LS increased from 5.0 (1997-1998) to 35.7 (2021-2022) per 100,000 person-years. Compared with the general female population, women with biopsy-verified vulvar LS had significantly increased rates of vulvar high-grade squamous precancer (SIR = 8.5; 95% CI: 7.2-10.0) and SCC (SIR = 16.2; 95% CI: 14.2-18.4). The SIRs of vulvar high-grade squamous precancer and SCC did not vary substantially according to length of follow-up. This nationwide and population-based study shows a 7-fold increase in the incidence of biopsy-verified vulvar LS since 1997. Data also show that women with biopsy-verified vulvar LS have 8.5 and 16 times higher than expected incidence of vulvar high-grade squamous precancer and SCC, respectively. The substantially increased incidence of vulvar high-grade squamous precancer and SCC following LS is important in relation to the clinical management and follow-up of LS patients.

Precursor lesions in familial and hereditary pancreatic cancer.

Infiltrating ductal adenocarcinoma of the pancreas, referred to here as "pancreatic cancer," is one of the deadliest of all of the solid malignancies. The five-year survival rate in the United States for individuals diagnosed today with pancreatic cancer is a dismal 12%. Many invasive cancers, including pancreatic cancer, however, arise from histologically and genetically well-characterized precursor lesions, and these precancers are curable. Precursor lesions therefore are an attractive target for early detection and treatment. This is particularly true for individuals with an increased risk of developing invasive cancer, such as individuals with a strong family history of pancreatic cancer, and individuals with a germline variant known to increase the risk of developing pancreatic cancer. There is therefore a need to understand the precursor lesions that can give rise to invasive pancreatic cancer in these individuals.

Calendar-period trends in cervical precancer and cancer diagnoses since the introduction of human papillomavirus and cytology co-testing into routine cervical cancer screening at Kaiser Permanente Northern California.

OBJECTIVES: The longer-term impact of introducing human papillomavirus (HPV) testing into routine cervical cancer screening on precancer and cancer rates by histologic type has not been well described. Calendar trends in diagnoses were examined using data from Kaiser Permanente Northern California, which introduced triennial HPV and cytology co-testing in 2003 for women aged ≥30 years. METHODS: We examined trends in cervical precancer (cervical intraepithelial neoplasia grade 3 [CIN3] and adenocarcinoma in situ [AIS]) and cancer (squamous cell carcinoma [SCC] and adenocarcinoma [ADC]) diagnoses per 1000 screened during 2003-2018. We examined ratios of squamous vs. glandular diagnoses (SCC:ADC and CIN3:AIS). RESULTS: CIN3 and AIS diagnoses increased approximately 2% and 3% annually, respectively (ptrend < 0.001 for both). While SCC diagnoses decreased by 5% per annually (ptrend < 0.001), ADC diagnoses did not change. These patterns were generally observed within each age group (30-39, 40-49, and 50-64 years). ADC diagnoses per 1000 screened did not change even among those who underwent co-testing starting in 2003-2006. SCC:ADC decreased from approximately 2.5:1 in 2003-2006 to 1.3:1 in 2015-2018 while the CIN3:AIS remained relatively constant, ∼10:1. CONCLUSIONS: Since its introduction at KPNC, co-testing increased the detection of CIN3 over time, which likely caused a subsequent reduction of SCC. However, there has been no observed decrease in ADC. One possible explanation for lack of effectiveness against ADC is the underdiagnosis of AIS. Novel strategies to identify and treat women at high risk of ADC need to be developed and clinically validated.

RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates.

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.