Human papillomavirus genotyping in high-grade vaginal intraepithelial neoplasia: A multicentric Italian study.

This study aimed to analyze the human papillomavirus (HPV) genotype distribution in a large cohort of high-grade vaginal intraepithelial neoplasia (VaIN) (vaginal HSIL, VaIN2/3) patients from two Italian referral centers. We included all patients with histologically confirmed VaIN2/3 from the Department of Surgical Sciences, Sant'Anna Hospital, University of Torino, Torino, Italy, and Ospedale Maggiore della Carità, Novara, Italy, between 2003 and 2022. After the histological evaluation of formalin-fixed paraffin-embedded samples, we performed HPV genotyping with VisionArray HPV Chip 1.0. We detected HPV DNA in 94.4% of VaIN2/3 (168/178), with HPV 16 as the most prevalent genotype, accounting for 51.8% of all infections, 41.2% of VaIN2 and 77.6% of VaIN3 cases. Other frequent genotypes were HPV 58 (8.3%, 10.9% of VaIN2 and 2.0% of VaIN3), HPV 73 (5.4%, 5.0% of VaIN2 and 6.1% of VaIN3), and HPV 31 (5.4%, 6.7% of VaIN2 and 2.0% of VaIN3). 73.2% of VaIN2/3 had a single HPV genotype infection and 26.8% a multiple infection (20.8% a double infection, 4.8% a triple infection, and 1.2% a quadruple infection). Single infection was more frequently present in VaIN3 than VaIN2 (81.6% vs. 69.8%). 69.1% of single infections and 73.3% of multiple infections had one or more genotypes covered by nine-valent HPV vaccine. HPV vaccination is expected to have a large impact on reducing the incidence of vaginal intraepithelial neoplasia.

Association between HPV infection and penile cancer and penile intraepithelial neoplasia: A retrospective observational study.

BACKGROUND: Penile cancer is rising in most European countries. Several risk factors have been identified, namely human papillomavirus (HPV) infection. However, the exact role of HPV in penile cancer carcinogenesis is still unknown. Clarifying the contribution of HPV in penile cancer is crucial as it may improve prevention and treatment strategies. OBJECTIVE: To describe the characteristics of patients with penile cancer and penile intraepithelial neoplasia (PeIN), evaluate the prevalence of HPV-DNA in tumour tissue and identify differences between patients with and without HPV-DNA. METHODS: A retrospective observational study including patients with histological diagnosis of penile squamous cell carcinoma (SCC) or PeIN between 2012 and 2021 in a university hospital was carried out. HPV analysis was performed using Anyplex™ II HPV28 Detection that detects and identifies 28 HPV types. (sensitivity of 95.9%). RESULTS: A total of 25 patients were included. Most of the tumours identified were invasive SCC (n = 11) and SCC in situ (PeIN 3) (n = 8). PeIN1/2 was found in the remaining six patients. HPV-DNA was tested in all tissue specimens and was detected in 18 of them. High risk HPV DNA was identified in all positive HPV samples, except one. HPV types included in the nonavalent HPV vaccine were identified in 16 of the 18 samples positive for HPV-DNA. Stratifying patients according to HPV-DNA detection, we found that patients with HPV-DNA were younger (57.5 years vs. 70 years, p = 0.047), less likely to have phimosis (5.8% vs. 42.9%, p = 0.022) and more likely to have PeIN lesions than invasive SCC (85.7% vs. 27.8%, p = 0.025). CONCLUSION: This study shows a prevalence of HPV-DNA in penile SCC and premalignant lesions of 45.5% and 92.9%, respectively. Identifying HPV involvement in SCC and PeIN pathology has the potential to guide treatment and enhance follow-up strategies.

Severe anal intraepithelial neoplasia trends and subsequent invasive anal cancer in the United States.

BACKGROUND: Anal intraepithelial neoplasia grade III is a precursor to squamous cell carcinoma of the anus for which rates are nearly 20-fold higher in people with HIV than in the general population in the United States. We describe trends in anal intraepithelial neoplasia grade III diagnosis and risk of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III by HIV status and sex. METHODS: We used data from a population-based linkage between cancer and HIV registries in 11 US states; Puerto Rico; and Washington, DC, during 1996-2019. We identified all individuals with a diagnosis of anal intraepithelial neoplasia grade III and determined their HIV status. We estimated the average annual percentage change of anal intraepithelial neoplasia grade III using Poisson regression stratified by HIV status and sex. We estimated the 5-year cumulative incidence of squamous cell carcinoma of the anus following an anal intraepithelial neoplasia grade III diagnosis stratified by sex, HIV status, and prior AIDS diagnosis. RESULTS: Among people with HIV, average annual percentage changes for anal intraepithelial neoplasia grade III were 15% (95% confidence interval [CI] = 12% to 17%) per year among females and 12% (95% CI = 11% to 14%) among males. Average annual percentage changes for those without HIV were 8% (95% CI = 7% to 8%) for females and 8% (95% CI = 6% to 9%) for males. Among people with HIV, a prior AIDS diagnosis was associated with a 2.7-fold (95% CI = 2.23 to 3.40) and 1.9-fold (95% CI = 1.72 to 2.02) increased risk of anal intraepithelial neoplasia grade III diagnosis for females and males, respectively. Five-year cumulative incidence of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III for people with HIV with a prior AIDS diagnosis were 3.4% and 3.7% for females and males, respectively. CONCLUSIONS: Rates of anal intraepithelial neoplasia grade III diagnoses have increased since 1996, particularly for people with HIV, likely influenced by increased screening. A prior AIDS diagnosis was strongly associated with risk of anal intraepithelial neoplasia grade III diagnosis.

Anal Dysplasia Screening in People Living with HIV: Long-Term Follow-Up in a Large Cohort from Northwest Spain.

Anal squamous cell carcinoma (SCC) is not a common disease in the general population, although its incidence is higher in people living with human immunodeficiency virus (PLWH). Anal SCC is caused by human papillomavirus (HPV) infection and arises from premalignant lesions termed squamous intraepithelial lesions (SILs). SIL surveillance programs are based on the early detection and treatment of SILs, especially those with a higher risk of transforming into cancer. An anal surveillance program has been under development in our institution since 2011. In this context, we performed a retrospective cohort study at the anal dysplasia unit of Álvaro-Cunqueiro Hospital (Spain). Epidemiological and clinical data were gathered from our Infectious Diseases Sample Collection (an open sample cohort including PLWH) from January 2011 to January 2022. A total of 493 PLWH were considered, 122 (24.7%) of whom were diagnosed with anal dysplasia at baseline, including 2 cases of anal SCC. Briefly, most of individuals were young men (median age, 38 years old) born in Spain (76%), whose vaccination rate before their inclusion in the program was scarce (<3%). Throughout the study period, 81 (16.4%) cases were diagnosed with high-grade squamous-intraepithelial lesions (HSILs) and 3 with anal SCC. At the baseline, severe immunosuppression (i.e., nadir CD4+ lymphocyte count below 200 cell/µL), and prior diagnosis of condyloma acuminata were more frequent within the group with SILs. Conversely, the baseline CD4+ lymphocyte count was similar among both groups. HPV-16 was related to a higher risk of HSILs (odds ratio: 2.76). At the end of the follow-up, 385 PLWH had been retained in care; one patient had died of anal cancer. Anal dysplasia was common (25% of cases), especially among patients infected by HPV-16, diagnosed with condyloma acuminata, and who were severely immunosuppressed. HPV-16 was the main risk factor for the presentation of HSILs.

The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model.

BACKGROUND & AIMS: Estimates on the progression of precursor lesions to pancreatic cancer (PC) are scarce. We used microsimulation modeling to gain insight into the natural disease course of PC and its precursors. This information is pivotal to explore the efficacy of PC screening. METHODS: A Microsimulation Screening Analysis model was developed in which pancreatic intraepithelial neoplasms and cysts can evolve from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to PC. The model was calibrated to Dutch PC incidence data and Japanese precursor prevalence data (autopsy cases without PC) and provides estimates of PC progression (precursor lesion onset and stage duration). RESULTS: Mean LGD state durations of cysts and pancreatic intraepithelial neoplasms were 15.8 years and 17.1 years, respectively. Mean HGD state duration was 5.8 years. For lesions that progress to PC, the mean duration was 4.8-4.9 years for LGD lesions and 4.0-4.1 years for HGD lesions. In 13.7% of individuals who developed PC, the HGD state lasted less than 1 year. The probability that an individual at age 50 years developed PC in the next 20 years was estimated to be 1.8% in the presence of any cyst and 6.1% in case of an LGD mucinous cyst. This 20-year PC risk was estimated to be 5.1% for individuals with an LGD pancreatic intraepithelial neoplasm. CONCLUSIONS: Mean duration of HGD lesions before development of PC was estimated to be 4.0 years. This implies a window of opportunity for screening, presuming the availability of a reliable diagnostic test. The probability that an LGD cyst will progress to cancer was predicted to be low.

Anal Intraepithelial Neoplasia and Anal Squamous Cell Carcinoma: Updates From the Last 3 Years.

ABSTRACT: In the last 3 years, new and relevant information has been published on anal cancer and anal precancerous lesions epidemiology, screening, treatment, and vaccination. This information will likely change prevention and treatment strategies for these patients in the upcoming years.

Impact of Human Papillomavirus Vaccine Against Anal Human Papillomavirus Infection, Anal Intraepithelial Neoplasia, and Recurrence of Anal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.

BACKGROUND: We sought to summarize human papillomavirus (HPV) vaccine efficacy/effectiveness (VE) against anal HPV infection and anal intraepithelial neoplasia (AIN). METHODS: We performed literature review and meta-analysis to estimate VE, stratified by age and analytic population (per-protocol efficacy [PPE] or intention-to-treat [ITT] population in clinical trials, or all participants in real-world studies). RESULTS: We identified 6 clinical trials and 8 real-world studies. In participants vaccinated at age ≤26 years (mainly human immunodeficiency virus [HIV]-negative individuals), significant VE against incident/prevalent anal HPV infection was reported in clinical trials, with a higher estimate in PPE (2 studies with 2390 participants; VE, 84% [95% confidence interval (CI), 77%-90%]; I2 = 0%) than ITT (2 studies with 4885 participants; 55%, 39%-67%; I2 = 46%) populations or in real-world studies (4 studies with 2375 participants; 77%, 40%-91%; I2 = 81%). HPV vaccination at age ≤26 years was associated with significant VE in preventing persistent anal HPV infection and AIN. No significant VE against anal HPV infection or AIN was found in persons vaccinated at age >26 years (mainly people living with HIV). CONCLUSIONS: There is strong evidence for high VE against anal HPV infection and AIN in HIV-negative individuals vaccinated at age ≤26 years. However, the lower impact in ITT than in PPE populations and the lack of significant effect in people living with HIV aged >26 years indicates that vaccines have the higher impact in populations with less sexual exposure to anal HPV.

Changes in cervical dysplasia, carcinoma in situ, and cervical cancer after expanding the National Cancer Screening Program to younger women in Korea.

The National Cancer Screening Program of South Korea for cervical cancer was expanded from women aged ≥30 years to women aged ≥20 years in 2016. This study investigated the effect of this policy on occurrence rates of cervical dysplasia, carcinoma in situ, and cervical cancer in women in their twenties. The National Health Information Database for the years 2012-19 was used. The outcome measures were monthly occurrence rates of cervical dysplasia, cervical carcinoma in situ, and cervical cancer. An interrupted time series analysis was performed to investigate whether the number of occurrences changed after policy implementation. For cervical dysplasia, a pre-intervention decreasing trend of 0.3243 per month (P-value < .0001) was found. The post-intervention trend did not differ significantly, although the slope increased at a rate of 0.4622 per month (P-value < .0001). For carcinoma in situ, a trend of increase at 0.0128 per month (P-value = .0099) was seen before policy implementation. The post-intervention trend did not escalate, but the slope showed an increasing trend of 0.0217 per month (P-value < .0001). For cervical cancer, no significant trend was present before intervention. Occurrences of cervical cancer escalated at a rate of 0.0406 per month (P-value < .0001) after policy implementation, and the slope also showed an increasing trend at a rate of 0.0394 per month (P-value < .0001). Expanding the target population for cervical cancer screening increased detection rates for cervical cancer in women aged between 20 and 29 years.

Prognosis of local invasive relapses after carcinoma in situ of the breast: a retrospective study from a population-based registry.

PURPOSE: The prognosis of local invasive recurrence (LIR) after prior carcinoma in situ (CIS) of the breast has not been widely studied and existing data are conflicting, especially considering the specific prognosis of this entity, compared to de novo invasive breast cancer (de novo IBC) and with LIR after primary IBC. METHODS: We designed a retrospective study using data from the specialized Côte d'Or Breast and Gynecological cancer registry, between 1998 and 2015, to compare outcomes between 3 matched groups of patients with localized IBC: patients with LIR following CIS (CIS-LIR), patients with de novo IBC (de novo IBC), and patients with LIR following a first IBC (IBC-LIR). Distant relapse-free (D-RFS), overall survival (OS), clinical, and treatment features between the 3 groups were studied. RESULTS: Among 8186 women initially diagnosed with IBC during our study period, we retrieved and matched 49 CIS-LIR to 49 IBC, and 46 IBC-LIR patients. At diagnosis, IBC/LIR in the 3 groups were mainly stage I, grade II, estrogen receptor-positive, and HER2 negative. Metastatic diseases at diagnosis were higher in CIS-LIR group. A majority of patients received adjuvant systemic treatment, with no statistically significant differences between the 3 groups. There was no significant difference between the 3 groups in terms of OS or D-RFS. CONCLUSION: LIR after CIS does not appear to impact per se on survival of IBC.

Characterization of patients with vulvar lichen sclerosus and association to vulvar carcinoma: a retrospective single center analysis.

PURPOSE: Lichen sclerosus (LS) is a benign, cutaneous, chronic inflammatory (autoimmunological) disease. The differentiated vulvar intraepithelial neoplasia (dVIN) accounts for a precursor lesion of vulvar squamous cell carcinoma and is often associated with lichen sclerosus. Although the association between lichen sclerosus and vulvar carcinoma has long been recognized, there is a lack of evidence in literature. METHODS: This retrospective study examined pseudonymized data of 499 women diagnosed with vulvar pathology between 2008 and 2020 at the Department of Gynaecology and Obstetrics of Hannover Medical School (MHH). Data were further stratified for the time of onset, location of disease, accompanying disease, HPV status and progression of disease into vulvar squamous cell carcinoma (VSCC). RESULTS: In total, 56 patients were diagnosed with vulvar lichen sclerosus. The mean onset of disease was at 60.3 years of age. After subdividing cases of diagnosed LS into those who did not develop vulvar carcinoma in their course and those who did, the ages at onset are 52.66 ± 17.35 and 68.41 ± 10.87, respectively. The incidence of vulvar cancer in women diagnosed with lichen sclerosus was 48.2%. Twenty-five patients reported a diagnosis of VIN in their self-reported history. CONCLUSIONS: In our retrospective study, we showed a trend between vulvar lichen sclerosus and VSCC. The difference between the two age groups of patients diagnosed with lichen sclerosus who developed vulvar carcinoma and those who did not is statistically significant. Our results highlight the importance to diagnose lichen sclerosus early to ensure adequate follow-up and prevent progression to VSCC.

Conventional cytologic diagnosis of human papillomavirus-induced anal intraepithelial neoplasia: The experience of a referral center in Rio de Janeiro, Brazil.

BACKGROUND: Screening of anal cancer is rarely available or performed in Brazil. This study analyzes the diagnostic performance of conventional cytology (CC) in the prevention of anal cancer in a coloproctology and gynecology outpatient clinics in a public hospital in Rio de Janeiro, Brazil. METHODS: From 2005 to 2017, 1066 conventional cytological samples were collected. We analyze the causes of unsatisfactory samples (11.3%) and compare the cytological diagnoses of 83 samples from persons living with HIV and persons not living with HIV and in specific situations, using as the gold standard high-resolution anoscopy or histopathology in cases biopsied within 6 months after cytology. RESULTS: The sensitivity of cytology with diagnosis of ASC-US for detection of anal intraepithelial neoplasia of any grade was 85%, specificity was 41%, positive and negative predictive values were 64% and 75%, respectively, and positive and negative likelihood ratios were 1.46 and 0.35, respectively. CONCLUSION: Conventional cytology available in resource-limited settings is a simple, noninvasive, low-cost method that proved feasible for outpatient screening of precursor lesions of the anal canal.

High-grade vaginal intraepithelial neoplasia and recurrence risk: analysis of an Italian regional referral center series.

PURPOSE: The main aim of this study was to investigate the long-term risk of disease recurrence in women treated for high-grade vaginal intraepithelial neoplasia (HG-VaIN). METHODS: We conducted a retrospective analysis on a cohort of 82 women diagnosed with HG-VaIN between 2010 and 2021 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. All women underwent either ablative treatment (CO2 laser ablation or electrocoagulation) or cold-knife excision. RESULTS: In our series, the recurrence rate following treatment was 17%. The 5-year cumulative probability of recurrence was 30.4% and the median time to recurrence was 15.5 months. None of the patients progressed to invasive vaginal cancer during follow-up. A concomitant cervical or vulvar intraepithelial lesion was significatively associated with an increased risk of recurrence (p = 0.006). CONCLUSIONS: The results of our study suggest that women with HG-VaIN are at high risk of developing disease recurrence after treatment, especially patients with a concomitant cervical or vulvar intraepithelial lesion. In these women strict monitoring is mandatory to obtain an early identification of recurrence.

Diagnosis and screening for anal intraepithelial neoplasia in Belgium: position statement.

Anal cancer is an uncommon malignancy, comprising only 2.5% of all gastrointestinal malignancies and similar to cervical cancer, the human papillomavirus (HPV) is responsible for the majority of anal cancers. Over the last decades there has been an up to 3-fold increased incidence seen in specific populations at risk such as persons living with HIV (PLWH), men who have sex with men (MSM), woman diagnosed with HPV-related gynaecological precancerous lesions or cancer, solid organ transplant recipients (SOTR) and patients with autoimmune diseases. Although international practice is evolving increasingly towards active screening for and treatment of anal cancer precursors in at-risk groups, currently no organised screening program is in effect in Belgium. Currently, differerent screening options as well as treatment modalities are available. Before commencing a nationwide organised screening program, essential decisions on screening strategies need to be made, based on both scientific as well as financial and logistical facts.

A Cross-Sectional Study of the Prevalence of Anal Dysplasia among Women with High-Grade Cervical, Vaginal, and Vulvar Dysplasia or Cancer: The PANDA Study.

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women. METHODS: This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA). RESULTS: 324 evaluable women were enrolled. Primary diagnosis was high-grade dysplasia/cancer of the cervix (77%), vagina (9%), and vulva (14%). Anal HR-HPV was detected in 92 patients (28%) and included HPV-16 in 24 (26%), HPV-18 in 6 (7%), and other HR-HPV types in 72 (78%) patients. Anal cytology was abnormal in 70 patients (23%) and included atypical squamous cells of undetermined significance (80%), low-grade squamous intraepithelial lesion (9%), high-grade intraepithelial lesion (HSIL; 1%), and atypical squamous cells-cannot rule out HSIL (10%). Of these patients, 55 (79%) underwent HRA. Anal biopsies were performed in 14 patients: 2 patients had anal intraepithelial neoplasia (AIN) 2/3, 1 patient had AIN 1, and 11 patients had negative biopsies. Both patients with AIN 2/3 had a history of cervical dysplasia. CONCLUSIONS: Our results suggest an elevated risk of anal HR-HPV infection and cytologic abnormalities in women with lower genital tract dysplasia/cancer. IMPACT: These results add to the growing body of evidence suggesting the need for evaluation of screening methods for anal dysplasia/cancer in this patient population to inform evidence-based screening recommendations.

Prevaccine Human Papillomavirus Status in Invasive and Intraepithelial Lesions of the Vulva in New Zealand Women.

OBJECTIVE: The human papillomavirus (HPV) vaccine, introduced in New Zealand (NZ) in 2008, is predicted to substantially lower the incidence of HPV-associated precancers and cancers. The aim of this study is to estimate the proportion of vulvar intraepithelial neoplasia (VIN) lesions and invasive vulvar squamous cell carcinomas (SCCV) attributable to HPV in NZ women treated by the Auckland Regional Gynecological Oncology Service, covering an estimated 50% of the NZ population. MATERIALS AND METHODS: Polymerase chain reaction and reverse hybridization were used to analyze retrospective histologically proven SCCV from 1990 to 2007 and VIN lesions from 2000 to 2007 for HPV content and genotype in a collaborative study with the Catalan Institute of Oncology. Immunohistochemistry for p16INK4a was performed on SCCV, which were attributed to HPV if both tested positive. RESULTS: Polymerase chain reaction testing for HPV content and genotype was performed on 66 VIN lesions (all high-grade squamous intraepithelial lesions) and 189 SCCV. In addition, p16 immunohistochemistry was performed on 168 of the 189 SCCV (88.9%) tested for HPV-DNA. Overall, 61 SCCV cases (36.3%) were attributed to HPV (HPV+/p16+), and 89 SCCV cases (53%) were considered to have developed independently of HPV (HPV-/p16-). Known high-risk HPV genotypes were present in 96.8% of HPV-DNA-positive vulvar high-grade squamous intraepithelial lesions and 98.4% of HPV-attributable SCCV. Human papillomavirus 16 represented the most common genotype in both. CONCLUSIONS: Overall, the HPV vaccine is likely to substantially alter the profile of SCCV in our region. The results provide a baseline assessment of the HPV status of vulvar neoplasia before the introduction of the HPV vaccine.

Vulvar Cancer Incidence in the United States and its Relationship to Human Papillomavirus Vaccinations, 2001-2018.

The human papillomavirus (HPV) vaccine was indicated for the prevention of vulvovaginal cancers in 2008, but its impact on the incidence of vulvar cancers within the US is unknown. To determine this, we conducted a secondary analysis of 88,942 vulvar cancer cases among women 20+ years old using the US Cancer Statistics 2001-2018 databases. Data were stratified by tumor behavior (in situ or invasive), age (20-44, 45-64, 65+ years old), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic), and US census region (Northeast, South, Midwest, West), and incidence rates and average annual percentage changes (AAPC) were calculated by group. Reversing previous trends, the incidence of vulvar carcinoma in situ significantly decreased between 2001 and 2018 among women from all age groups, races/ethnicities, and regions (combined AAPC,  -4.3; 95% confidence interval (CI), -4.7 to -3.8). The incidence of invasive vulvar squamous cell carcinoma decreased significantly among 20- to 44-year-old women (AAPC, -0.8; 95% CI, -1.3 to -0.3), but significantly increased among those 45 to 64 (AAPC, 2.3; 95% CI, 1.8-2.8) and 65+ years old (AAPC, 1.2; 95% CI, 1.1-1.4). Regardless of tumor behavior, incidence was highest among non-Hispanic Whites and the Midwest region. Overall, the significant declines in vulvar carcinoma in situ among all ages, as well as invasive vulvar cancer among younger women, are encouraging and complement other recent data suggesting HPV vaccinations are already reducing anal and cervical cancer incidence. Over time, further declines in vulvar carcinoma incidence are likely as uptake and completion rates of the HPV vaccine increase in the US. PREVENTION RELEVANCE: We found evidence that HPV vaccinations likely contributed to a decrease in the incidences of vulvar carcinoma in situ and invasive vulvar carcinoma among 20- to 44-year-old women between 2001 and 2018. Our data add to the growing evidence that HPV vaccinations are reducing the incidence of HPV-related anogenital cancers.

Incidence of Pancreatic Intraepithelial Neoplasia in an Autopsy Series.

OBJECTIVES: Pancreatic intraepithelial neoplasia (PanIN) is the currently preferred designation for putative preneoplastic changes in the pancreas. There are few data for the incidence of PanIN in the general population. Our goal was to determine the incidence of PanIN in a large group of pancreases obtained at autopsy. METHODS: Slides stained with hematoxylin and eosin were scanned to count PanIN. RESULTS: We found multiple PanINs in most pancreases and at least 1 in 86.4% of 154 pancreases when multiple slides (8-12) from each were examined. The average age at autopsy was 62 years, and 90% of the patients were 40 years or older. Several questions were raised by our observations. Should a minimum size be defined for classification as PanIN? Do PanINs occur in lesions that apparently arise from acinar to ductal metaplasia? Does squamous metaplasia in PanIN have any special significance, and do purely squamous lesions have preneoplastic significance? CONCLUSIONS: We conclude that the incidence of PanIN is higher than previously reported.

Active surveillance for non-muscle-invasive bladder cancer: fallacy or opportunity?

PURPOSE OF REVIEW: This review aims to analyze the current place of active surveillance (AS) in non-muscle-invasive bladder cancer (NMIBC). RECENT FINDINGS: A growing body of evidence suggests that AS protocols for pTa low-grade (TaLG) NMIBC are safe and feasible. However, current guidelines have not implemented AS due to a lack of high-quality data. Available studies included pTa tumors, with only one study excluding pT1-NMIBC. Inclusion/exclusion criteria were heterogeneously defined based on tumor volume, number of tumors, carcinoma in situ (CIS), or high-grade (HG) NMIBC. Tumor volume <10 mm and <5 lesions were used as cut-offs. Positive urinary cytology (UC) or cancer-related symptoms precluded inclusion. Surveillance within the first year consisted of quarterly cystoscopy. AS stopped upon the presence of cancer-related symptoms, change in tumor morphology, positive UC, or patient's request. With a median time on AS of 16 months, two-thirds of the patients failed AS. Progression to muscle-invasive bladder cancer (MIBC) was rare and occurred only in patients with pT1-NIMBC at inclusion. SUMMARY: AS in NMIBC is an attractive concept in the era of personalized medicine, but strong evidence is still awaited. A more precise definition of patient inclusion, follow-up, and failure criteria is required to improve its implementation in daily clinical practice.

Anal intraepithelial neoplasia screening in patients with human immunodeficiency virus infection.

INTRODUCTION: the incidence of anal cancer has increased in recent years, making screening and early detection of anal intraepithelial neoplasia (AIN) a necessity in patients at risk. METHODS: a descriptive observational study of homosexual patients (MSM) or women with cervical intraepithelial neoplasia (CIN) III, with human immunodeficiency virus (HIV) infection, included in an AIN detection screening program was carried out between March 2016 and September 2019. RESULTS: we have performed 695 anal smears, 156 with results of LSIL (low-grade lesion) or HSIL (high-grade lesion) (22.4 %), and 116 high resolution anoscopy (HRA), 75.3 % of patients with altered cytology. We have 403 biopsies, being 84 % pathological, 197 biopsies of AIN I (49 %), 96 of AIN II and III (24 %), 44 condylomas (11 %) and the rest (16 %), normal mucosa. CONCLUSION: the high prevalence of premalignant lesions and the improvement in the staging of lesions after treatment recommend this protocol.

Incidence of penile intraepithelial neoplasia and treatment strategies in Sweden 2000-2019.

OBJECTIVES: To analyse the incidence, treatment strategies and complications associated with penile intraepithelial neoplasia (PeIN) in Sweden over a period of 20 years. MATERIALS AND METHODS: Data on PeIN from the Swedish National Penile Cancer Register were analysed regarding treatment in relation to age, size of the PeIN lesion, localization of the PeIN lesion and complications using chi-squared tests and logistic regression. The incidence of PeIN was calculated and age-standardized according to the European Standard population. RESULTS: Between 2000 and 2019 a total of 1113 PeIN cases were reported. The age-standardized incidence of PeIN was 1.40 per 100 000 men (95% confidence interval [CI] 1.32-1.49). An increase in incidence over time was seen, with a standardized incidence rate of 2.37 (95% CI 1.56-3.70) in 2019 compared to the baseline year, 2000. Surgical or topical treatments were given in 75.0% and 14.6% of cases, respectively. The complication rate was higher in laser surgery (12.1%, 7/58) compared to local surgery (4.6%, 16/348; P = 0.03) with an age-adjusted odds ratio (OR) of 2.82 (95% CI 1.10-7.19; P = 0.03). Local surgery was more common than laser surgery in the last 5 years compared to the first 5 years of the study period: OR 5.75 (95% CI 2.94-11.27). Treatments with imiquimod and topical 5-fluorouracil (5-FU) were more common than destructive methods such as photodynamic therapy, cryotherapy, curettage and electrocautery in the last 5 years compared to the first 5 years: OR 9.48 (95% CI 2.29-39.24). CONCLUSIONS: A twofold increase in the age-standardized incidence of PeIN was seen in Sweden over 20 years. Complications were three times more common in laser surgery compared to local surgery. Changes in treatment showed an increase of treatment strategies such as local surgery and treatment with imiquimod and topical 5-FU over time.