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.

Multizonal anogenital neoplasia in women: a cohort analysis.

BACKGROUND: There is currently a lack of information on full anogenital evaluation of women with a previous history of anogenital neoplasia. METHODS: Retrospective analysis of the Homerton Anogenital Neoplasia Service records from January 2012 to March 2017, to identify all new referrals of women with previous anogenital neoplasia, who had had at least one complete examination of all anogenital sites. Multizonal anogenital disease (MZD) was defined as the presence of high-grade squamous intraepithelial lesions (HSIL)/carcinoma concurrently at two or more of the following sites/zones: perianus, anal canal, vulva, vagina or cervix. RESULTS: 253 women were included, mean age was 47 (SD=15) years and median duration of follow-up was 12 (IQR=21) months. Fifty-six women (22%) were diagnosed with MZD at first assessment and/or during follow-up. Current smokers (RR=1.84, 95% CI 1.21-2.79, p=0.004) and women on immunodulators/immunosuppressive drugs (RR=2.57, 95% CI 1.72-3.86, p<0.001) had an increased risk for MZD. The risk was lower for women without a previous history of anogenital high-grade lesions/cancer compared to those with this history (RR=0.06, 95% CI 0.01-0.45, p=0.006). CONCLUSIONS: Multizonal assessment was important to diagnose occult areas of disease and should be especially considered in current smokers, pharmacologically immunocompromised and those with a previous history of anogenital HSIL/cancer.

Anal cancer and precancerous lesions: a call for improvement.

Anal squamous cell carcinoma is the most common type of anal cancer and is largely associated with anal human papillomavirus infection. The incidence of anal squamous cell carcinoma is increasing, and although still uncommon in the general population, a high incidence has been noted in specific population groups (eg, patients with HIV, men who have sex with men [MSM], recipients of solid organ transplants, women with genital neoplasia, and patients with systemic lupus erythematosus or inflammatory bowel disease). The higher incidence among individuals who are HIV-positive makes anal squamous cell carcinoma one of the most common non-AIDS-defining cancers among HIV-positive individuals. Anal cancer screening in high-risk groups aims to detect high-grade squamous intraepithelial lesions, which are considered anal precancerous lesions, and for which identification can provide an opportunity for prevention. A blind anal cytology is normally the first screening method, and for patients with abnormal results, this approach can be followed by an examination of the anal canal and perianal area under magnification, along with staining-a technique known as high-resolution anoscopy. Digital anorectal examination can enable early anal cancer detection. Several societies are in favour of screening for HIV-positive MSM and recipients of transplants. There are no current recommendations for screening of anal precancerous lesions via endoscopy, but in high-risk groups, a careful observation of the squamocolumnar junction should be attempted. Several treatments can be used to treat high-grade squamous intraepithelial lesions, including argon plasma coagulation or radiofrequency ablation, which are largely limited by high recurrence rates. Gastroenterologists need to be aware of anal squamous cell carcinoma and anal precancerous lesions, given that patients at high risk are frequently encountered in the gastroenterology department. We summarise simple procedures that can help in early anal squamous cell carcinoma detection.

High-Resolution Anoscopy Surveillance After Anal Squamous Cell Carcinoma: High-Grade Squamous Intraepithelial Lesion Detection and Treatment May Influence Local Recurrence.

BACKGROUND: Local recurrence is a significant risk after anal squamous cell carcinoma. OBJECTIVES: This study aimed to examine the occurrence of high-grade squamous intraepithelial lesions and local recurrence after anal cancer at surveillance with high-resolution anoscopy. DESIGN: This is a retrospective observational study. SETTING: This study was conducted at an anogenital neoplasia referral center. PATIENTS: There were 76 anal/perianal cancers from 1998 to 2018. Sixty-three patients were eligible and 3 were excluded, for a total of 60 patients; 35 of 60 (58%) patients were male. INTERVENTION: High-resolution anoscopy after chemoradiation or excision only for anal squamous cell carcinoma was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were local recurrence and high-grade squamous intraepithelial lesion detection rates. RESULTS: Sixty patients, 27% HIV positive, underwent surveillance over a median 42 (range 7-240) months of follow-up. Seven had had a prior local recurrence at study entry so were analyzed separately. Thirty of 53 underwent chemoradiation (57%) and 23 of 53 underwent excision alone (43%); 33 had perianal cancer and 20 had anal cancer. Ten of 30 of the chemoradiation group had had stage 1 (33%) disease in comparison with 22 of 23 of the excision only group (96%, p < 0.001). OUTCOMES: High-grade squamous intraepithelial lesions were detected in 4 of 30 (13%) patients after chemoradiation and in 17 of 23 (74%) patients after excision only (p < 0.001). Twenty of 21 (95%) high-grade lesions were treated with ablation. Six of 7 (86%) patients with prior local recurrence had high-grade squamous intraepithelial lesions over a median of 21 months follow-up. One local recurrence (T1N0M0) occurred during surveillance after primary chemoradiation (0.56/1000 person-months), none occurred after excision only, and 2 of 7 with prior local recurrence developed further local recurrence (6.86/1000 person-months). All 3 local recurrences occurred after treatment of high-grade squamous intraepithelial lesions. There were no metastases, abdominoperineal excisions, or deaths from anal squamous cell carcinoma. LIMITATIONS: Retrospective data were used for this study. CONCLUSIONS: High-grade squamous intraepithelial lesions after anal squamous cell carcinoma are more common after excision only than after chemoradiation. Local recurrence is low in this high-resolution anoscopy surveillance group in which high-grade squamous intraepithelial disease was ablated. Excision of small perianal cancers appears safe; however, a subset of patients is at excess risk. See Video Abstract at http://links.lww.com/DCR/B285. VIGILANCIA POR ANOSCOPÍA DE ALTA RESOLUCIÓN EN CASOS DE CARCINOMA ANAL A CÉLULAS ESCAMOSAS: LA DETECCIÓN Y TRATAMIENTO DE UNA LESIÓN INTRAEPITELIAL ESCAMOSA DE ALTO GRADO (HSIL) PUEDE INFLUIR EN LA RECURRENCIA LOCAL: La recurrencia local tiene un riesgo significativo después del carcinoma anal a células escamosas.Evaluar la aparición de lesiones intraepiteliales escamosas de alto grado (HSIL) y su recurrencia local durante la vigilancia con anoscopía de alta resolución en casos de cancer anal.Estudio observacional retrospectivo.Centro de referencia de neoplasia anogenital.Se diagnosticaron 76 cánceres anales / perianales entre 1998 y 2018. Un total de 63 pacientes fueron elegidos, 3 excluidos (n = 60), 35/60 (58%) fueron varones.Anoscopía de alta resolución después de la quimio-radioterapia, o solo excisión en casos de carcinoma anal a células escamosas.Recurrencia local primaria y tasas de detección de lesión intraepitelial escamosa de alto grado.Sesenta pacientes, 27% VIH positivos, fueron sometidos a vigilancia durante una mediana de 42 (rango 7-240) meses de seguimiento. Siete habían tenido una recurrencia local antes de ser incluidos en el estudio, por lo que se analizaron por separado. Treinta de 53 se sometieron a quimio-radioterapia (57%) y 23/53 solo a excisión (43%). 33 eran lesiones perianales, 20 de canal anal. 10/30 del grupo de quimio-radioterpia se encontraban en Fase 1 (33%) comparados con 22/23 del grupo de excisión (96%, p <0.001).Se detectaron lesiones intraepiteliales escamosas de alto grado en 4/30 (13%) después de la quimio-radioterapia, y en 17/23 (74%) solo después de la excisión (p < 0.001). 20/21 (95%) lesiones de alto grado fueron tratadas con ablación. Seis de siete (86%) con recurrencia local previa tenían lesiones intraepiteliales escamosas de alto grado durante una mediana de seguimiento de 21 meses. Se produjo una recurrencia local (T1N0M0) durante la vigilancia después de la quimio-radioterapia primaria (0.56/1000 persona-meses), ninguna después de la excisión sola y 2/7 con recurrencia local previa desarrollaron una recurrencia local adicional (6.86/1000 persona-meses). Las 3 recidivas locales ocurrieron después del tratamiento de las lesiones intraepiteliales escamosas de alto grado. No hubieron metástasis, excisiones abdominoperineales o muertes por carcinoma anal a células escamosas.Datos retrospectivos.Las lesiones intraepiteliales escamosas de alto grado en casos de carcinoma escamocelular anal son más comunes después de la excisión sola que después de la quimio-radioterapia. La recurrencia local es baja en este grupo de vigilancia de anoscopía de alta resolución en el que se retiró la enfermedad intraepitelial escamosa de alto grado. La excisión de pequeños cánceres perianales parece segura; sin embargo, un subconjunto de pacientes tiene un riesgo excesivo. Consulte Video Resumen en http://links.lww.com/DCR/B285. (Traducción-Dr. Xavier Delgadillo).

Anal High-Grade Squamous Intraepithelial Lesions in Pharmacologically Immunocompromised Patients Followed in a Referral Center.

BACKGROUND: Information is lacking regarding anal/perianal precancerous lesions in referral cohorts of pharmacologically immunocompromised patients. OBJECTIVE: The aim of this study is to evaluate the prevalence of anal/perianal high-grade squamous intraepithelial lesions in a referral cohort of patients on immunomodulator/immunosuppressive medications, who were assessed and followed with high-resolution anoscopy. DESIGN: This is a retrospective study. SETTING: This study was conducted in a single anal neoplasia service from January 2012 to June 2017. PATIENTS: Patients on chronic immunomodulator/immunosuppressive medications were included. Cases of concomitant immunosuppression due to HIV infection were excluded, and immunosuppression due to chemotherapy was not considered for this analysis. INTERVENTION: High-resolution anoscopy was performed. MAIN OUTCOME: The primary outcome measured was the prevalence of anal/perianal high-grade squamous intraepithelial lesions in a referral cohort of pharmacologically immunocompromised patients. RESULTS: Fifty-four patients were included, of whom 40 were women (74%), with a mean age of 48 ± 17 years. A total of 232 high-resolution anoscopy examinations were performed in this cohort. At the first evaluation, 28 patients (52%) were diagnosed with anal and/or perianal high-grade squamous intraepithelial lesions (including 2 cases of perianal squamous cell carcinoma); 11 cases (20%) were new diagnoses. Ten of 46 patients (22%) with follow-up developed a new lesion (high-grade/cancer) during a median follow-up period of 17 (interquartile range, 6-28) months. Overall, 37 patients (69%) in our cohort had anal/perianal high-grade squamous intraepithelial lesions ever diagnosed (including previous history, first visit, and follow-up); 5 patients had perianal squamous cell carcinoma. At our center, 6% of the new referrals were known to be pharmacologically immunocompromised patients. LIMITATIONS: The retrospective nature of this study, the heterogeneity of the cohort, and the absence of human papillomavirus testing were limitations of this study. CONCLUSIONS: The presence of anal and/or perianal high-grade squamous intraepithelial lesions or cancer detected by high-resolution anoscopy in this referral population was high, and the detection of new lesions suggests that long-term follow-up is needed. Patients on immunomodulator/immunosuppressive drugs represented only a small percentage of the new referrals to our center. See Video Abstract at http://links.lww.com/DCR/A748.

The acceptability of high resolution anoscopy examination in patients attending a tertiary referral centre.

BACKGROUND: High resolution anoscopy (HRA) examination is regarded as the best method for the management of anal high grade squamous intraepithelial lesions to prevent anal squamous carcinoma. However, little is known about the acceptability of this procedure. This analysis looks at patient experience of HRA examination and ablative treatment under local anaesthetic. METHODS: Patients took part in anonymised feedback of their experience immediately after their HRA examinations and/or treatments. A standard questionnaire was used that included assessment of pain and overall satisfaction scores as well as willingness to undergo future HRA examinations. RESULTS: Four hundred four (89.4%) responses were received and all responses were analysed. The group consisted of 119 females (29.4%) and 261 males (64.6%) with median age of 45 years (IQR = 19) and 45 years (IQR = 21) respectively, and included 58 new cases, 53 treatment cases and 202 surveillance cases. 158 patients (39.1%) had at least one biopsy during their visits. The median pain score was 2 [Inter Quartile Range (IQR) 3] on a visual analogue scale of 0 to 10, where 0 indicated no pain / discomfort and 10 indicated severe pain. The median pain score was 2 (IQR 2) in men and 4 (IQR = 3) in women [Dunn's Test = 4.3, p < 0.0001] and 3 (IQR 4.5) in treatment cases. Problematic pain defined as a pain score of ≥7 occurred more frequently in women (14%) than in men (6%), [Chi square test (chi2) = 5.6, p = 0.02]. Patient satisfaction with the care they received, measured on a scale of 0 (not happy) to 10 (very happy) found the median score to be 10 with 76% reporting a score of 10. Out of 360 responses, 98% of women and 99% of men said that they would be willing to have a future HRA examination. CONCLUSIONS: In this cohort, the overall pain scores were low and similar across appointment types. However, women had a higher pain score, including troublesome pain levels. Despite this, both women and men were equally satisfied with their care and were willing to have a future examination. The results of the analysis show that the procedure is acceptable to patient groups. A small number of women may need general anaesthesia for their examinations/treatment.

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.

A randomised clinical trial (RCT) of a symbiotic mixture in patients with irritable bowel syndrome (IBS): effects on symptoms, colonic transit and quality of life.

PURPOSE: The aim of this study is to test in a double-blinded, randomised placebo-controlled study the effects of a commercially available multi-strain symbiotic mixture on symptoms, colonic transit and quality of life in irritable bowel syndrome (IBS) patients who meet Rome III criteria. BACKGROUND: There is only one other double-blinded RCT on a single-strain symbiotic mixture in IBS. METHODS: This is a double-blinded, randomised placebo-controlled study of a symbiotic mixture (Probinul, 5 g bid) over 4 weeks after 2 weeks of run-in. The primary endpoints were global satisfactory relief of abdominal flatulence and bloating. Responders were patients who reported at least 50 % of the weeks of treatment with global satisfactory relief. The secondary endpoints were change in abdominal bloating, flatulence, pain and urgency by a 100-mm visual analog scale, stool frequency and bowel functions on validated adjectival scales (Bristol Scale and sense of incomplete evacuation). Pre- and post-treatment colonic transit time (Metcalf) and quality of life (SF-36) were assessed. RESULTS: Sixty-four IBS patients (symbiotic n = 32, 64 % females, mean age 38.7 ± 12.6 years) were studied. This symbiotic mixture reduced flatulence over a 4-week period of treatment (repeated-measures analysis of covariance, p < 0.05). Proportions of responders were not significantly different between groups. At the end of the treatment, a longer rectosigmoid transit time and a significant improvement in most SF-36 scores were observed in the symbiotic group. CONCLUSIONS: This symbiotic mixture has shown a beneficial effect in decreasing the severity of flatulence in IBS patients, a lack of adverse events and a good side-effect profile; however, it failed to achieve an improvement in global satisfactory relief of abdominal flatulence and bloating. Further studies are warranted.

From menarche to menopause: the fertile life span of celiac women.

OBJECTIVE: We evaluated menopause-associated disorders and fertile life span in women with celiac disease (CD) under untreated conditions and after long-term treatment with a gluten-free diet. METHODS: The participants were 33 women with CD after menopause (untreated CD group), 25 celiac women consuming a gluten-free diet at least 10 years before menopause (treated CD group), and 45 healthy volunteers (control group). The Menopause Rating Scale questionnaire was used to gather information on menopause-associated disorders. The International Physical Activity Questionnaire was used to acquire information on physical activity. RESULTS: Untreated celiac women had a shorter duration of fertile life span than did the control women because of an older age of menarche and a younger age of menopause (P < 0.01). The scores for hot flushes, muscle/joint problems, and irritability were higher in untreated celiac women than in the control women (higher by 49.4%, 121.4%, and 58.6%, respectively; P < 0.05). In comparison with untreated CD, long-lasting treatment of CD was not associated with a significant difference in the duration of fertile life span, but was only associated with a significant reduction in muscle/joint problems (a reduction of 47.1%; P < 0.05). CONCLUSIONS: Late menarche and early menopause causes a shorter fertile period in untreated celiac women compared with control women. A gluten-free diet that started at least 10 years before menopause prolongs the fertile life span of celiac women. The perception of intensity of hot flushes and irritability is more severe in untreated celiac women than in controls. Low physical exercise and/or poorer quality of life frequently reported by untreated celiac women might be the cause of reduced discomfort tolerance, thus increasing the subjective perception of menopausal symptoms.