Anal High-risk Human Papillomavirus Infection, Squamous Intraepithelial Lesions, and Anal Cancer in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Ulcerative colitis [UC] and Crohn's disease [CD] can be associated with severe comorbidities, namely opportunistic infections and malignancies. We present the first systematic review and meta-analysis evaluating the burden of anal human papillomavirus disease in patients with UC and CD. METHODS: PubMed, Web of Science, and Scopus were searched until November 2022. Meta-analyses were performed using random effects models. The protocol was recorded at PROSPERO register with the number CRD42022356728. RESULTS: Six studies, including 78 711 patients with UC with a total follow-up of 518 969 person-years, described the anal cancer incidence rate. For anal cancer incidence rate in CD, six studies were selected, including 56 845 patients with a total follow-up of 671 899 person-years. The incidence of anal cancer was 10.2 [95% CI 4.3 - 23.7] per 100 000 person-years in UC and 7.7 [3.5 - 17.1] per 100 000 person-years in CD. A subgroup analysis of anal cancer in perianal CD, including 7105 patients, was calculated with incidence of 19.6 [12.2 - 31.6] per 100 000 person-years [three studies included]. Few studies described prevalence of anal cytological abnormalities [four studies including 349 patients] or high-risk human papillomavirus [three studies including 210 patients], with high heterogeneity. Prevalence of cytological abnormalities or high-risk human papillomavirus was not associated with pharmacological immunosuppression in the studies included. CONCLUSION: The incidence of anal cancer is higher in UC than in CD, with the exception of perianal CD. There are limited and heterogeneous data on anal high-risk human papillomavirus infection and squamous intraepithelial lesions prevalence in this population.

High-risk human papilloma virus, precancerous lesions and cancer in anal condylomas.

INTRODUCTION: Anal condylomas are associated with human papillomavirus (HPV) infection and are a risk factor for anal squamous cell carcinoma (SCC). OBJECTIVE: To conduct a meta-analysis evaluating the prevalence of anal high-risk HPV, high-grade squamous intraepithelial lesions (HSIL) and SCC in patients with condylomas. The standardized incidence ratio (SIR) and the incidence rate of anal SCC were also calculated. METHODS: Three electronic databases were searched until April 2020. Meta-analyses were performed using random effects models. RESULTS: Pooled prevalence estimate of high-risk HPV (HR-HPV) in anal condylomas was 40.2% (21.0-63.1) in immunocompromised and 16.4% (10.7-24.3) in nonimmunocompromised patients, with an odds ratio (OR) of 3.79 (1.51-9.52, P = 0.005) for immunocompromised patients. HR-HPV in condylomas with HSIL was 73.8% (39.1-92.5) and in non-HSIL cases was 17.7% (9.6-30.2), corresponding to an OR of 12.33 (2.97-51.21, P = 0.001) for those with HSIL. The prevalence of HSIL in condylomas was 24.0% (16.4-33.7) in immunocompromised and 11.8% (7.2-18.8) in nonimmunocompromised patients, with an OR of 2.51 (1.72-3.65, P < 0.001) for immunocompromised patients. The overall prevalence of anal SCC in anal condylomas was 0.3% (0.0-1.7). The SIR of anal SCC was 10.7 (8.5-13.5), 20.1 (14.4-28.2) in men and 7.7 (5.6-10.5) in women. The overall incidence rate of anal SCC was 6.5 per 100 000 person-years (3.6-11.7), 12.7 (9.1-17.8) in men and 4.7 (1.7-13) in women. CONCLUSION: Patients with a history of anal condylomas have a high risk of anal SCC, especially men. The prevalence of HR-HPV and HSIL in condylomas from immunocompromised patients is high. This information can change patient follow-up and treatment.

Performance of human papillomavirus DNA detection in residual specimens taken for Chlamydia trachomatis and Neisseria gonorrhoeae nucleic acid amplification testing in men who have sex with men.

OBJECTIVES: Rectal swab specimens, either alone or pooled with first-void urine (FVU) and pharyngeal swab specimens, are used to test for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection in men who have sex with men (MSM). Following introduction of human papillomavirus (HPV) vaccination for MSM attending UK sexual health services (SHSs), HPV testing of residual CT/NG test specimens has been proposed to monitor HPV prevalence in this population. Performance of HPV detection in such specimens has not been evaluated previously. METHODS: MSM attending a UK SHS provided three specimens: (1) rectal swab for CT/NG, (2) pooled rectal/pharyngeal/FVU specimen for CT/NG and (3) dedicated anal swab for HPV. Specimen 3 and residual material from specimens 1 and 2 were tested for type-specific HPV DNA. HPV detection was by an in-house multiplex PCR and luminex-based genotyping assay. RESULTS: A total of 129 MSM were recruited with a mean age of 38.1 years; 24% were HIV-positive. Of the 129 MSM, 92 (71%) had any type-specific HPV DNA in ≥1 specimen; 80 (62%) had high risk (HR) HPV. Of 123 participants with sufficient residual pooled and dedicated specimens, 70 (56.9%) had detectable HPV on both, and 40 (32.5%) were negative on both; overall concordance was 89% (95% CI 83% to 94%), and kappa statistic was 0.78 (95% CI 0.66 to 0.89). Pooled samples had a 4.1% (95% CI -1.9% to 10.0%) higher test positivity rate than dedicated samples.Of 125 participants with sufficient residual rectal and specimens, 74 (59.2%) had detectable HPV on both, and 36 (28.8%) were negative on both; overall concordance was 88% (95% CI 81% to 93%), and kappa statistic was 0.74 (95% CI 0.61 to 0.86). Residual rectal samples had 5.6% (95%CI -0.6% to 11.8%) higher test positivity than dedicated samples. CONCLUSIONS: We observed high concordance between the dedicated and residual STI test specimens. Our data support the strategy of testing residual specimens for HPV prevalence monitoring in MSM to evaluate the impact of the targeted vaccination programme.

Burden of anal squamous cell carcinoma, squamous intraepithelial lesions and HPV16 infection in solid organ transplant recipients: A systematic review and meta-analysis.

The number of solid organ transplant recipients (SOTR), and their life expectancy, is increasing, with higher risk for long-term complications from immunosuppression. We carried out a systematic review describing the burden of anal squamous cell carcinoma (SCC), and its surrogates, in SOTR. We conducted mixed effect model-based meta-analyses evaluating incidence of anal SCC (standardized incidence ratio [SIR] vs general population, and absolute incidence rate [IR]), prevalence of anal squamous abnormalities, and human papillomavirus (HPV) 16. Generalized I2 statistics were calculated, quantifying heterogeneity. Anal SCC incidence in SOTR was elevated vs the general population (pooled SIR = 6.8, 95% confidence interval [CI], 4.3-10.9; 6 studies including 241 106 SOTR; I2  = 82.3%), with an absolute IR of 12.3 (95% CI, 10.4-14.7) per 100 000 person-years (5 studies including 1 079 489 person-years; I2  = 0%). Prevalence of abnormal anal cytology was 12.9% (95% CI, 9.2%-17.7%; 6 studies including 328 SOTR; I2  = 17.4%). For histology, the pooled prevalence estimate of anal squamous intraepithelial lesions was 22.4% (95% CI, 17.3%-28.5%; 3 studies including 214 SOTR; I2  = 0%), with 4.7% (95% CI, 2.5%-8.5%; I2  = 0%) high-grade squamous intraepithelial lesions. Pooled anal HPV16 prevalence was 3.6% (95% CI, 1.6%-7.8%; 4 studies including 254 SOTR; I2  = 17.6%). There was substantial and consistent evidence of elevated anal SCC incidence in SOTR.

Expression of microRNAs 16, 20a, 150 and 155 in anal squamous intraepithelial lesions from high-risk groups.

Anal squamous intraepithelial lesions (ASIL) or anal intraepithelial neoplasia (AIN) are precancerous lesions. microRNAs (miRNAs) have been implicated in cervical carcinogenesis, but have never been assessed in anal precancerous lesions. Our aim was to evaluate the expression of miR-16, miR-20a, miR-150 and miR-155 in several grades of ASIL obtained from high-risk patients, submitted to anal cancer screening from July 2016 to January 2017. Lesions were classified according to the Lower Anogenital Squamous Terminology (LAST) in low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL), and the AIN classification in AIN1, AIN2 and AIN3. A hundred and five biopsies were obtained from 60 patients. Ten samples were negative (9.5%), 63 were LSIL (60%) and 32 were HSIL (30.5%) according to the LAST. Twenty seven (26%) were negative for dysplasia, 46 were classified as AIN1 (44%), 14 as AIN2 (13%) and 18 as AIN3 (17%) according to the AIN classification. There was no statistically significant difference in the fold expression of miR-16, miR-20a, miR-150 and miR-155, according to either classification. Although non- significant, there was an increasing trend in the miR-155 fold expression from negative samples to HSIL, with the highest fold expression increase in both LSIL and HSIL compared to the other miRNAs.

Performance of Anal Cytology Compared With High-Resolution Anoscopy and Histology in Women With Lower Anogenital Tract Neoplasia.

Background: Information on the performance of anal cytology in women who are high risk for human papillomavirus-related lesions and the factors that might influence cytology are largely lacking. Methods: Retrospective study including all new referrals of women with a previous history of anogenital neoplasia from January 2012 to July 2017, with concomitant anal cytology and high-resolution anoscopy with or without biopsies. Results: Six hundred and thirty six anal cytology samples and 323 biopsies obtained from 278 women were included. Overall sensitivity and specificity of "any abnormality" on anal cytology to predict any abnormality in histology was 47% (95% confidence interval [CI], 41%-54%) and 84% (95% CI, 73%-91%), respectively. For detecting high-grade squamous intraepithelial lesions (HSIL)/cancer, sensitivity was 71% (95% CI, 61%-79%) and specificity was 73% (95% CI, 66%-79%). There was a poor concordance between cytological and histological grades (κ = 0.147). Cytology had a higher sensitivity to predict HSIL/cancer in immunosuppressed vs nonimmunosuppressed patients (92% vs 60%, P = .002). The sensitivity for HSIL detection was higher when 2 or more quadrants were affected compared with 1 (86% vs 57%, P = .006). A previous history of vulvar HSIL/cancer (odds ratio [OR], 1.71, 1.08-2.73; P = .023), immunosuppression (OR, 1.88, 1.17-3.03; P = .009), and concomitant genital HSIL/cancer (OR, 2.51, 1.47-4.29; P = .001) were risk factors for abnormal cytology. Conclusions: Women characteristics can influence the performance of anal cytology. The sensitivity for detecting anal HSIL/cancer was higher in those immunosuppressed and with more extensive disease.