Anal intraepithelial neoplasia screening in women from the largest center for lower genital tract disease in China.

This study aimed to provide comprehensive clinical screening data for anal intraepithelial neoplasia (AIN). This study included 312 patients who underwent high-resolution anoscopy (HRA) examinations between January 1, 2020 and April 15, 2024. Clinical data, including demographic information, clinical history, cytology/high-risk human papilloma virus (hrHPV) results, and HRA records, were analyzed. The median age of all patients was 42 years (interquartile range: 33-52 years). Approximately 26.3% reported a history of VIN2/3+, 13.5% had a history of VaIN2/3+, 29.8% had a history of CIN2/3+, 44.6% had persistent cervical HPV16 infection, and 12.5% had immune suppression. Among the 312 patients, 14.4% were diagnosed with AIN2/3, 25.0% with AIN1 and 60.6% were normal. Anal cytological abnormalities were found in 41.3% of all patients, with a significantly higher rate in AIN2/3 patients than in ≤AIN1, 71.1% versus 36.3%, p < 0.001. The hrHPV positivity rate was 89.7%, with HPV16 being the most prevalent. The complete agreement rate for HRA impressions was 79.5%. Multi-variable analysis revealed immune suppression (odds ratio [OR]: 3.47, 95% confidence interval [CI]: 1.42-8.5) and VIN2/3+ (OR: 2.82, 95% CI: 1.27-6.28) were independent risk factors for AIN2/3. Abnormal cytology results (OR: 3.3, 95% CI: 1.52-7.17) and anal HPV16 infection (OR: 3.2, 95% CI: 1.26-8.12) demonstrated similar ORs for AIN2/3. Early screening for AIN2/3+ is crucial in Chinese women with lower genital tract precancerous and cancerous lesions, particularly in those with VIN2/3+ and immune suppression.

Prognostic value of PD-L1 expression in patients with anal cancer: a meta-analysis.

Background: The present meta-analysis was performed to evaluate the prognostic and clinicopathological significance of PD-L1 in anal cancer (AC). Methods: Hazard ratios (HRs) and 95% CIs regarding overall survival (OS) and progression-free survival (PFS) were calculated based on PD-L1 levels. Results: According to the combined data, PD-L1 showed no significant relationship with OS (HR = 0.76; 95% CI = 0.35-1.67; p = 0.502) or PFS (HR = 0.88; 95% CI = 0.35-2.33; p = 0.789) in patients with AC. Based on subgroup analysis, PD-L1 overexpression significantly predicted prolonged OS (HR = 0.38; 95% CI = 0.17-0.84; p = 0.017) in tumor node metastasis stages I-III and inferior PFS (HR = 2.73; 95% CI = 1.32-5.65; p = 0.007) in patients with stage I-IV AC. Conclusion: PD-L1 level assessed by immunohistochemistry did not significantly predict survival outcomes in AC cases.

[Box: see text].

Accurate detection of copy number aberrations in FFPE samples using the mFAST-SeqS approach.

BACKGROUND: Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS and challenges of small biopsies ask for an alternative to the untargeted NGS approaches. The mFAST-SeqS approach, relying on LINE-1 repeat amplification, showed a good correlation with Shallow-seq to detect CNA in blood samples. In the present study, we evaluated whether mFAST-SeqS is suitable to assess CNA in small formalin-fixed paraffin-embedded (FFPE) tissue specimens, using vulva and anal HPV-related lesions. METHODS: Seventy-two FFPE samples, including 36 control samples (19 vulva;17 anal) for threshold setting and 36 samples (24 vulva; 12 anal) for clinical evaluation, were analyzed by mFAST-SeqS. CNA in vulva and anal lesions were determined by calculating genome-wide and chromosome arm-specific z-scores in comparison with the respective control samples. Sixteen samples were also analyzed with the conventional Shallow-seq approach. RESULTS: Genome-wide z-scores increased with the severity of disease, with highest values being found in cancers. In vulva samples median and inter quartile ranges [IQR] were 1[0-2] in normal tissues (n = 4), 3[1-7] in premalignant lesions (n = 9) and 21[13-48] in cancers (n = 10). In anal samples, median [IQR] were 0[0-1] in normal tissues (n = 4), 14[6-38] in premalignant lesions (n = 4) and 18[9-31] in cancers (n = 4). At threshold 4, all controls were CNA negative, while 8/13 premalignant lesions and 12/14 cancers were CNA positive. CNA captured by mFAST-SeqS were mostly also found by Shallow-seq. CONCLUSION: mFAST-SeqS is easy to perform, requires less DNA and less sequencing reads reducing costs, thereby providing a good alternative for Shallow-seq to determine CNA in small FFPE samples.

[Anal canal cancer : epidemiology, work-up, treatment and perspective]. / Le cancer du canal anal : épidémiologie, bilan, traitement et futur.

Although rare, around 2 % of digestive tumours, anal canal tumours remain a pathology that should not be neglected. These are frequently underdiagnosed due to the affected region and the symptoms that can be confused with more common and benign pathologies such as haemorrhoids or anal fissures. The treatment of these tumours is mainly based on radio-chemotherapy to avoid heavy surgical treatment which remains the salvage option. This article aims to review the epidemiology, diagnosis, management, monitoring and future developments for these cancers.

Bien que rares (environ 2 % des tumeurs digestives), les tumeurs du canal anal restent une pathologie à ne pas négliger. Elles sont souvent sous-diagnostiquées en raison de la région touchée et de la symptomatologie non spécifique, et confondues avec des pathologies plus fréquentes et bénignes comme des hémorroïdes ou des fissures anales. Le traitement de ces tumeurs repose principalement sur la radio-chimiothérapie, afin d'éviter une prise en charge chirurgicale lourde qui reste l'option de sauvetage. Cet article a pour but de passer en revue l'épidémiologie, le diagnostic, la prise en charge, le suivi et les futurs développements pour ces cancers.

Comparative evaluation of Anyplex II HPV28 and Allplex HPV28 molecular assays for human papillomavirus detection and genotyping in anogenital cancer screening.

Persistent infection with high-risk human papillomavirus (HPV) is recognized as the main cause for the development of anogenital cancers. This study prospectively evaluated the diagnostic performance of the novel Allplex-HPV28 assay with the Anyplex-II-HPV28 to detect and genotype HPV in 234 consecutive swabs and 32 biopsies of the anogenital tract from 265 patients with atypical findings in cytomorphological screening. Agreement in HPV-DNA detection between the Anyplex-II and Allplex-HPV28 assays was 99%. There was a notable diversity in the HPV-virome, with the most prevalent high-risk HPV types being 16, 53, 66, and 68. The agreement rates for detecting these genotypes exceeded 93% between the Anyplex-II and Allplex-HPV28 assays. Discrepancies in test results were solely noted for Anyplex-II-HPV28 results with a low signal intensity of "+", and for Allplex-HPV28 results with cycle thresholds of ≥36. The semi-quantitative analysis of HPV-DNA loads showed significant agreement between the Anyplex-II-HPV28 and Allplex-HPV28 assays (p < 0.001). Furthermore, HPV-DNA detection rates and mean HPV-DNA loads significantly correlated with the grade of abnormal changes identified in cytopathological assessment, being highest in cases of HSIL, condyloma accuminatum, and squamous cell carcinoma. Overall agreement rates for detecting specific HPV-types among the Anyplex-II and Allplex-HPV28 assays exceeded 99.5% in cases of atypical squamous cells, condyloma accuminatum, and squamous cell carcinoma. The novel Allplex-HPV28 assay shows good diagnostic performance in detecting and genotyping HPV commonly associated with anogenital cancers. Consequently, this assay could offer substantial potential for incorporation into future molecular screening programs for anogenital cancers in clinical settings.

Condyloma and Anal Dysplasia.

Anal intraepithelial neoplasia (AIN) are precancerous lesions and are sequela of human papilloma virus (HPV) infection. AIN is classified as low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion. Screening with anal cytology and anoscopy should be considered for high-risk populations. Diagnosis is made through high resolution anaoscopy and biopsy. Options for treatment include ablation and several topical therapies; however, recurrence rates are high for all treatment options, and an ongoing surveillance is necessary to prevent progression to anal squamous cell carcinoma. HPV vaccination is recommended to prevent disease.

Methylation markers for anal cancer screening: A repeated cross-sectional analysis of people living with HIV, 2015-2016.

People living with HIV (PLWH) are at highest risk of anal cancer and will benefit from optimized screening for early disease detection. We compared host DNA methylation markers in high-grade squamous intraepithelial lesions (HSIL) versus samples negative for intraepithelial lesions (NILM) or low-grade intraepithelial lesions (LSIL) in PLWH. We recruited PLWH identifying as male aged ≥18 years undergoing high-resolution anoscopy (HRA) in Seattle, Washington, 2015-2016. Anal brush samples were collected for HPV detection, genotyping, and pyrosequencing methylation (host genes ASCL1, PAX1, FMN2, and ATP10A); clinical data were abstracted from medical records. We assessed associations between methylation and presence and extent of HSIL using generalized estimating equation logistic regression, adjusting for age, CD4 count and HIV viral load. Marker panels using HPV DNA and methylation were also evaluated to predict prevalent HSIL. We analyzed 125 samples from 85 participants (mean age 50.1; standard deviation 11.0 years). ASCL1 (adjusted odds ratio [aOR] per 1 unit increase mean percent methylation: 1.07, 95% CI: 1.01-1.13) and FMN2 (aOR per 1 unit increase mean percent methylation: 1.14, 95% CI: 1.08-1.20) methylation were significantly associated with HSIL versus NILM/LSIL. ASCL1 (aOR: 1.06, 95% CI: 1.01-1.11) and FMN2 (aOR: 1.13, 95% CI: 1.08-1.17) methylation were positively associated with increasing HSIL extent. A panel combining methylation (ASCL1 and FMN2) and HPV DNA (HPV16, HPV18, and HPV31) demonstrated best balance of sensitivity (78.2%) and specificity (73.9%) for HSIL detection compared with methylation or HPV alone. Increasing levels of DNA methylation of ASCL1 and FMN2 were positively associated with HSIL detection in PLWH. Host gene methylation testing shows promise for HSIL screening and triage.

Preventive Care for Men Who Have Sex With Men.

Men who have sex with men (MSM) is an inclusive term used to refer to phenotypic males who have insertive or receptive sex (penile-anal or penile-oral) with other phenotypic males, including people who are transgender or have other gender identities. MSM may report their sexual orientation as homosexual, bisexual, heterosexual, or something else, but this stated sexual orientation may not align with their sexual attraction or behaviors. Several health conditions disproportionately affect MSM compared with age-matched heterosexual men, including HIV infection, anal cancer, syphilis, and depression. Clinicians should use culturally sensitive questions to obtain a comprehensive sexual history and assess sexual risk. MSM should receive regular screening for HIV, hepatitis B and C, gonorrhea, chlamydia, and syphilis. Vaccinations for hepatitis A and B and human papillomavirus should be offered. MSM may benefit from preexposure prophylaxis to prevent HIV infection, postexposure prophylaxis to reduce the risk of HIV transmission, and counseling on safer sexual practices. Screening for anal cancer associated with human papillomavirus may be performed by digital anal rectal examination, although the optimal screening strategy has yet to be determined. Clinicians should also consider more frequent screenings for mental health issues in the MSM population because the rates of depression, suicide, substance use, and other psychosocial issues are higher than those of the general population.

The influence of home versus clinic anal human papillomavirus sampling on high-resolution anoscopy uptake in the Prevent Anal Cancer Self-Swab Study.

Background Anal cancer disproportionately affects sexual and gender minority individuals living with HIV. High-resolution anoscopy (HRA) is an in-clinic procedure to detect precancerous anal lesions and cancer, yet prospective data on factors associated with HRA attendance are lacking. We examined whether anal HPV sampling at home versus in a clinic impacts HRA uptake and assessed HRA acceptability. Methods Sexual and gender minority individuals were randomised to home-based self-sampling or clinical sampling. All were asked to attend in-clinic HRA 1year later. We regressed HRA attendance on study arm using multivariable Poisson regression and assessed HRA acceptability using χ 2 tests. Results A total of 62.8% of 196 participants who engaged in screening attended HRA. Although not significant (P =0.13), a higher proportion of participants who engaged in clinic-based screening attended HRA (68.5%) compared to home-based participants (57.9%). Overall, HRA uptake was higher among participants with anal cytology history (aRR 1.40, 95% CI 1.07-1.82), and lower among participants preferring a versatile anal sex position versus insertive (aRR 0.70, 95% CI 0.53-0.91), but did not differ by race or HIV serostatus. In the clinic arm, persons living with HIV had lower HRA attendance (42.9%) versus HIV-negative participants (73.3%) (P =0.02) and Black non-Hispanic participants had lower HRA attendance (41.7%) than White non-Hispanic participants (73.1%), (P =0.04). No differences in attendance by race or HIV status were observed in the home arm. Conclusions HRA uptake differed significantly by race and HIV status in the clinic arm but not the home arm.

Multiple carcinomas in a woman with HIV infection: a case report and literature review.

Non-acquired immunodeficiency syndrome-defining cancers (NADCs) are malignancies in persons living with human immunodeficiency virus (PLWHIV) and are not primarily due to the host's immunodeficiency. There is renewed clinical interest in long-term morbidities in PLWHIV as well as malignancies that occur in this population. We herein describe a 36-year-old woman with a 2-year history of an anal wound and right breast mass. She had been diagnosed with HIV infection prior to the development of these lesions. Clinical and laboratory evaluations led to diagnoses of breast and anal cancers. Chemotherapy and antiretroviral therapy were begun, but the patient discontinued these treatments early and was lost to follow-up. NADCs will continue to be a major clinical issue as the global population ages. This presentation of two NADCs (breast and anal cancers) in a PLWHIV further highlights the burden of multiple malignancies on the depleted health of HIV-infected patients. Early identification and treatment of HIV upon patients' presentation to cancer care sites and screening for NADCs at HIV/AIDS care sites are recommended for improved outcomes.

Interobserver agreement in the interpretation of anal cytology.

BACKGROUND: Anal cytology represents a tool for anal cancer screening in high-risk populations. In addition to accuracy, the reproducibility of the interpretation is of key importance. The authors evaluated the agreement of anal cytologic interpretation between two cytopathologists. METHODS: Liquid-based cytologic slides from human immunodeficiency virus (HIV)-negative men who have sex with men (MSM) were evaluated by two readers with at least 10 years of expertise in cervical cytology. Cases with a discordant interpretation were reviewed, and a consensus was reached. Human papillomavirus (HPV) genotyping was performed using a proprietary HPV genotyping test. Unweighted and weighted Cohen kappa and 95% confidence interval (CI) values were calculated. RESULTS: Overall, 713 slides that were adequate for interpretation were evaluated (MSM: median age, 33 years). An HPV test was performed on 620 samples (87.0%). Considering a dichotomous interpretation (negative for intraepithelial lesion or malignancy vs. atypical squamous cells of undetermined significance or worse), the crude agreement between the two readers was 93.3% (kappa = 0.82; 95% CI, 0.77-0.87). Once a consensus for discordant cases was reached, the best agreement was found for the negative for intraepithelial lesion or malignancy category (511 of 528 samples; 96.8%), whereas the atypical squamous cells of undetermined significance category showed the lowest agreement (90 of 117 samples, 76.9%). Considering the individual cytologic categories, overall agreement was 92.1% (kappa = 0.85; 95% CI, 0.81-0.89). The discordant interpretations were not associated with high-risk HPV infection, HPV16 infection, or MSM age. CONCLUSIONS: The results indicating excellent interobserver agreement in this study substantiate the use of anal cytology in the setting of human immunodeficiency virus-negative MSM.

Assessing the Potential of HPV16 E6 Seroprevalence as a Biomarker for Anal Dysplasia and Cancer Screening-A Systematic Review and Meta-Analysis.

Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex with men (MSM) living with HIV underscore the need for effective screening. While high-resolution anoscopy-guided biopsy is the gold standard, limited provider availability poses a challenge. This has spurred interest in identifying biomarkers for improved AC prevention. Antibodies against HPV16 oncoprotein E6, known as markers for cervical and oropharyngeal cancers, are the focus of the current study. The systematic review and meta-analysis included six studies meeting inclusion criteria, assessing HPV16 E6 seroprevalence in individuals with anal HSIL or AC. A two-step meta-analysis estimated pooled odds ratios and 95% confidence intervals (CI) for HPV16 E6 seroprevalence and HSIL or AC. Pooled prevalence, sensitivity, specificity, and diagnostic odds ratios were also calculated. This meta-analysis revealed a 3.6-fold increased risk of HSIL for HPV16 E6 seropositive individuals, escalating to a 26.1-fold risk increase for AC. Pooled specificity and sensitivity indicated a high specificity (0.99; 95%CI: 0.99, 0.99) but lower sensitivity (0.19; 95%CI: 0.10, 0.34) for HPV16 E6 serostatus as an AC biomarker. In conclusion, while HPV16 E6 seroprevalence demonstrates specificity as a potential biomarker for HPV-related AC, its utility as a standalone screening tool may be limited. Instead, it could serve effectively as a confirmation test, particularly in high-risk populations, alongside other diagnostic methods. Further research is imperative to explore HPV16 E6 seroconversion dynamics and alternative screening algorithms.

Access to High-Resolution Anoscopy Among Persons With HIV and Abnormal Anal Cytology Results.

This cross-sectional study evaluates use and availability of follow-up anoscopy among persons at highest risk for anal cancer.