Performance of Different Follow-Up Strategies and Genotype-Based Recurrence Risk After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion.

OBJECTIVE: Our aim was to evaluate the performance of different follow-up strategies after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3, including human papillomavirus (HPV) detection, cytology, or colposcopy, as well as their combinations. Additionally, we compared the influence of the persistence of HPV 16/18 versus that of other high-risk HPV genotypes (HR-HPV) in the recurrence risk. METHODS: Retrospective register-based study, including women who had an excision of the transformation zone for CIN2 or CIN3 at our institution, between January 2011 and December 2022. The outcome assessed was histopathological recurrence/persistence of CIN2 or worse. RESULTS: Of the 721 women included, 6.8% (49/721) had recurrence/persistence. The sensitivity, specificity, and positive and negative predictive values of the HPV test were 97.4%, 80%, 22.3%, and 99.8%, respectively, whereas for cotesting (HR-HPV and cytology), 86.8%, 90.1%, 34.4%, and 99.1%, respectively. The referral rates for colposcopy were 24.3% and 14.2%, respectively. The sensitivity of colposcopy was low (40.0%).Women who were initially positive for non-16/18 genotypes at baseline who became HPV16/18 positive during follow-up, had a statistically significant increased risk of CIN2 or worse, compared with those who tested positive only for other HR-HPV genotypes during both stages (hazard ratio = 4.98; 95% CI = 1.66-14.91). CONCLUSIONS: Human papillomavirus testing is the best strategy for follow-up after treatment of cervical HSIL. The addition of cytology triage decreases by more than 40% the referrals for colposcopy, without significantly missing cases of recurrence/persistence. Human papillomavirus 16/18 in the follow-up, regardless of being previously positive, is associated with higher risk of recurrence/persistence of HSIL.

Factors associated with human papillomavirus persistence after loop electrosurgical excision procedure in patients with cervical squamous intraepithelial lesion.

AIM: To seek the high-risk factors of human papillomavirus (HPV) persistence and residual lesion or recurrence after loop electrosurgical excision procedure (LEEP) focus on the predictive value of intraoperative human papilloma virus (IOP-HPV) testing. METHODS: Intraoperative endocervical sample was obtained with a cytobrush from the remained cervix of 292 patients immediately after LEEP. HPV Genotyping was performed using a polymerase chain reaction technique. All patients followed by HPV genotyping and cytology every 3-6 months. The IOP-HPV testing results and possible risk factors such as age, cytology grade, menopause status, margin involvement, preoperative HPV status, and cervical lesion grade were assessed in predicting persistence of HPV and residual lesion or recurrence after surgery. RESULTS: There were 61 (20.9%) patients presented persistent HPV infection. Multivariate analyses showed that IOP-HPV positive, post-menopause and preoperative HPV multiplex infection was strongly associated with HPV persistence after LEEP, IOP-HPV positive and post-menopause was also associated with residua or recurrent disease after LEEP. CONCLUSIONS: IOP-HPV positive, post-menopause, and preoperative HPV multiplex infection are independent predictors of HPV persistence in patients with cervical squamous intraepithelial lesion treated by LEEP. IOP-HPV test is a new approach that may potentially allow for early identification of patients at high risk of HPV persistence and residua or recurrent disease after LEEP, thereby possibly facilitate an attenuated follow-up schedule for negative patients those at low risk of persistent HPV infection.

Rational of topical photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) for treatment of endocervical canal low-grade squamous intraepithelial lesion with high-risk human papillomavirus infection.

BACKGROUND: The detection and continuous monitoring of low-grade squamous intraepithelial lesions (LSIL) within the endocervical canal pose considerable challenges, and the effectiveness of ablation treatment is also constrained. In this context, the potential efficacy of 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) in targeting these concealed lesions merits exploration. The present study undertakes a comprehensive analysis of the clinical effectiveness and safety aspects associated with the utilization of 5-ALA PDT. METHODS: A retrospective analysis was conducted on a cohort of 13 patients who were diagnosed with LSIL within the endocervical canal, concomitant with high-risk human papillomavirus (hrHPV) infection. These patients were subjected to treatment with 5-ALA PDT and subsequently monitored over a period of 3-6 months following the intervention. RESULTS: The study cohort comprised 13 patients, among whom 4 presented with isolated lesions within the endocervical canal, 5 exhibited LSIL involving both the endocervical canal and the cervix vaginal portion, 3 displayed LSIL within the endocervical canal in conjunction with vaginal involvement, and 1 patient demonstrated lesions across all three of these anatomical sites. All identified lesions underwent therapeutic intervention via 5-ALA PDT. Before treatment initiation, 9 patients returned positive results in the liquid-based cytologic test (LBC), 4 displayed concurrent multiple hrHPV infections, and 5 manifested infections specifically with HPV 16/18. Subsequent to the application of 5-ALA PDT, regression was observed in the LBC results of all patients, with only 3 individuals retaining a singular type of hrHPV infection. Adverse reactions following treatment encompassed mild aberrant vaginal secretions and mild to moderately pronounced distending abdominal discomfort, all of which were remitted within a span of 7 days. CONCLUSIONS: Within the context of LSIL within the endocervical canal in association with hrHPV infection, the findings affirm the efficacy and safety of 5-ALA PDT as a viable therapeutic modality.

Betapapillomaviruses in p16-Negative Vulvar Intraepithelial Lesions Associated with Squamous Cell Carcinoma.

Approximately 40% of vulvar squamous cell carcinoma (vSCC) cases are etiologically associated with high-risk human papillomaviruses (HPVs) of the alpha genera (α-HPV) that cause other anogenital cancers; however, the etiology of α-HPV-negative vSCC is poorly understood. HPVs of the beta genera (ß-HPV) are risk factors for cutaneous squamous cell carcinoma (cSCC) and may be related to carcinomas originating in other cutaneous sites such as the vulva. In this study, we investigate the presence of ß-HPVs, with an emphasis on p16-negative squamous lesions adjacent to vSCC. We subjected 28 vulvar squamous intraepithelial lesions adjacent to vSCC for comprehensive HPV genotyping, p16 and p53 immunohistochemistry, and consensus morphology review. Selected cases were subjected to qPCR and RNA in situ hybridization. Clinical data were obtained from medical records. ß-HPV DNA was detected in eight of ten p16-negative lesions and three of fourteen p16-positive high-grade squamous intraepithelial lesions. The HPV DNA loads in vulvar squamous intraepithelial lesions ranged between less than 1 HPV DNA copy per cell to more than 100 HPV DNA copies per cell. This is, to the best of our knowledge, the first report of the association of p16-negative vulvar intraepithelial squamous lesions with detection of ß-HPVs. These findings expand possible etiologic mechanisms that may contribute to p16-negative lesions of the vulva.

Detection of cervical high-grade squamous intraepithelial lesions and assessing diagnostic performance of colposcopy among women with oncogenic HPV.

BACKGROUND: HPV screening tests may improve cervical cancer risk stratification and better guide decisions about follow-up with colposcopy/biopsy. This study aimed to estimate the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with oncogenic HPV types and evaluate the performance of colposcopy in the diagnosis of histologic CIN2 + at Putuo Hospital, Shanghai, China. METHODS: This cross-sectional survey was conducted from February 2020 to December 2022 among women who were referred to colposcopy. Women with high-risk (HR) HPV-positive, cytology testing and colposcopy-directed biopsy were included. RESULTS: Univariate and multivariate analysis indicated that high-grade colposcopic impression ((OR, 17.61%, 95%CI: 11.54-26.85%) was associated with the highest risk for detecting CIN2+, followed by HSIL + cytology (OR, 6.90%, 95%CI: 3.56-13.37%) and HPV16/18 positive (OR, 2.91%, 95%CI: 2.12-3.99%). Overall, CIN2 + was detected in 14.6% of 2007 women. HPV16/18 had higher CIN2 + risks than other HR-HPV genotypes (30.1% vs. 10.2%, P<0.001). Among women with low-grade cytology, 24.1% had CIN2+, and the risks for HPV16/18 (58.2%) were higher than for other HR-HPV(16.8%). For those with high-grade cytology, there was no significant difference between HPV groups ( 75.0% vs. 72.9%, P > 0.05). The diagnostic performance of colposcopy in diagnosis of CIN2 + by senior and junior colposcopists was comparable. CONCLUSIONS: The results indicated that referral to colposcopy is recommended in managing women with HR-HPV positive, and colposcopic impressions provide key clues for identification CIN2+.

Clinical Efficacy and Safety of AdV-tk Gene Therapy for Patients with Cervical Squamous Intraepithelial Lesion: A Prospective Study.

Cervical cancer is the fourth most common type of cancer for women in 2020, and many more women have cervical precancerous lesion-squamous intraepithelial lesion (SIL). Early treatment of cervical SIL to reverse or delay its progression is an important approach to reduce the incidence of cervical cancer. The efficacy and safety of adenovirus-based vectors expressing the thymidine kinase gene (AdV-tk) in the treatment of multiple types of cancers shows promise for its use in gynecology. We aim to provide relevant clinical efficacy and safety data after introducing AdV-tk for the treatment of cervical SIL for the first time through this prospective study. We conducted a maximum of 6 sessions to administer AdV-tk gene therapy to 23 patients (mean age: 35 years old) with cervical low-/high-grade SIL (LSIL/HSIL) who were enrolled from August 2015 to April 2018 and analyzed the clinical characteristics and follow-up outcomes (mean follow-up period: 7.3 months). The present study consisted of 17 patients (73.9%) with cervical HSIL and 6 patients with LSIL confirmed by colposcopy-directed biopsy. We observed an overall histological remission and regression rate of 87.0% (20/23, 95% confidence interval [95% CI]: 73.2-100, p < 0.001) after AdV-tk gene therapy. Eight patients (34.8%) were detected with human papillomavirus (HPV) 16/18 subtypes and 13 patients were found to be positive with at least one of the other 13 high-risk HPV (HR-HPV) subtypes, while 2 patients did not have any of the 15 HR-HPV subtypes. The overall clearance rate of HR-HPV was 76.2% (16/21, 95% CI: 58.0-94.4, p = 0.016) after AdV-tk gene therapy. For safety evaluation, no severe complications were reported in any of the 23 patients. The most commonly reported symptom was fever in 52.2% (12/23) of patients and all symptoms were fully resolved after symptomatic treatment. Our data indicate that AdV-tk gene therapy has high efficacy and safety in the treatment of cervical SIL among gynecological patients. Our findings provide clinical evidence on the potential promotion and application of AdV-tk in the treatment of cervical SIL, and potentially for cervical cancer, among gynecological patients.

High Specificity of HPV Cell-Free DNA Tests in Persons With HIV for the Detection of HPV-Related Cancer.

INTRODUCTION: Persons with HIV (PWH) experience high rates of human papillomavirus (HPV)-associated cancers compared with the general population. Plasma HPV cell-free DNA (cfDNA) tests are sensitive in patients with known HPV-associated cancers. It is not known whether these tests can screen for invasive cancers in populations with high burdens of nonmalignant HPV disease such as PWH. It was not known whether HPV infection and/or noninvasive anal high-grade squamous intraepithelial lesions (HSIL) alone in this population would result in detectable HPV cfDNA, which would result in a high number of false positives if HPV cfDNA is used to screen for invasive cancers. METHODS: We conducted a prospective study of PWH in 2 cohorts: 20 without anal HSIL and 20 with anal HSIL. We tested anal and vaginal swabs for HPV infection, and HPV genotyped the biopsies of anal HSIL. Finally, we performed HPV cfDNA droplet digital polymerase chain reaction to test for HPV16/18/33 from plasma samples. RESULTS: In the combined cohorts, the median age was 56 years, 12.5% were cisgender women, and none had detectable HIV. In total, 84.6% had prevalent anovaginal HPV infection, including 10 participants with HPV16, 13 with HPV18, and 2 with HPV33 infections. Five and 2 participants had HPV16 and HPV33 detected in anal HSIL, respectively. Despite the high prevalence of HPV infection and anal HSIL, no participant had HPV16/18/33 detectable cfDNA by droplet digital polymerase chain reaction. CONCLUSIONS: These results provide a strong rationale for investigating the use of HPV cfDNA in a screening setting for suspected HPV-related invasive cancers in PWH.

Role of Low-Risk HPV PCR Monoinfection in Screening for HSIL and Anal Cancer in Men Who Have Sex with Men Living with HIV.

To determine the value of low-risk human papillomavirus (HPV) PCR to screen for "high-grade anal squamous intraepithelial lesion and anal cancer" (HSIL-plus), rate of patients with low-grade anal squamous intraepithelial lesion (LSIL) progressing to HSIL-plus, and progression-related factors. Prospective, longitudinal study of consecutive MSM-LHIV attended between May 2010 and December 2021 and followed for 43 months (IQR: 12-76). HIV-related variables were gathered at baseline, performing anal cytology for HPV detection/genotyping, thin-layer cytological study, and high-resolution anoscopy (HRA). Follow-up was annual when HRA was normal or LSIL, and post-treatment in cases of HSIL-plus, re-evaluating sexual behavior, viral-immunological status, and HPV infection of anal mucosa. The 493 participants had mean age of 36 years: CD4 nadir < 200 cells/uL in 23.1%, virological failure in 4.1%, and tetravalent HPV vaccine > 5 years earlier in 15%. HSIL-plus was ruled out in patients with monoinfection by low-risk HPV genotype and normal cytology (100% sensitivity, 91.9% specificity, PPV 2.9%, and NPV 100%). Progression from LISL to HSIL-plus occurred in 4.27% of patients within 12 months (IQR: 12-12): risk factors were acquisition of high-risk (HR: 4.15; 95% CI: 1.14-15.03) and low-risk (HR: 3.68 95% CI: 1.04-12.94) HPV genotypes, specifically genotype 6 (HR: 4.47, 95% CI: 1.34-14.91), and history of AIDS (HR: 5.81 95% CI: 1.78-18.92). Monoinfection by LR-HPV genotypes in patients with normal cytology is not associated with anal cancer or precursor lesions. Progression from LSIL to HSIL-plus, observed in <5% of patients, was related to acquisition of HR and LR HPV genotypes, especially 6, and a history of AIDS.

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.

A Pilot Study of a Screening Program for Human Papillomavirus-Related Squamous Intraepithelial Lesion and Malignancy in Gynecologic Oncology Patients.

OBJECTIVE: Human papillomavirus (HPV)-related squamous intraepithelial lesion (SIL) or malignancy is associated with a significantly increased risk of second-site SIL or malignancy. The primary objective of this study was to determine the feasibility and acceptability of concurrent anal, cervical, and vulvovaginal screening in patients with a history of HPV-related gynecologic high-grade SIL or malignancy. The secondary objective was to assess subjects' knowledge regarding HPV screening and risks. METHODS: Women with high-grade cervical, vulvar, or vaginal SIL or malignancy were enrolled during a 1-year pilot period. Subjects with cervical SIL or malignancy underwent vulvar examination and anoscopy. Subjects with vulvovaginal SIL or malignancy underwent Pap test if indicated and anoscopy. Appropriate referrals were made for abnormal findings. Feasibility was assessed by compliance using study acceptance rate, screening procedure adherence, and referral adherence. Acceptability was assessed using a Likert-scaled question after completion of screening procedures. RESULTS: One hundred three women with a diagnosis of high-grade vulvovaginal or cervical SIL or carcinoma were approached regarding study enrollment; of these, 74 (71.8%) enrolled. The median score on the HPV knowledge assessment was 8.1 ± 1.6 (max score 10). Seventy-three (98.6%) of 74 patients rated the screening procedures as acceptable (score of 5/5). On examination, 14 (18.9%) subjects had abnormalities noted; 7 (9.5%) were referred for colorectal surgical evaluation, and 6/7 (85.7%) were compliant with their referral appointments. CONCLUSIONS: Screening examinations for other HPV-related SILs and malignancies, including Pap tests, vulvovaginal inspection, and anoscopy, are acceptable to patients, with abnormal findings in almost 1 in 5 women.

Cervical High-Grade Squamous Intraepithelial Lesion Burden and Standard of Care Treatment Effectiveness and Safety in the United States, 2008-2018: The EACH-WOMAN Project.

OBJECTIVE: Management of cervical high-grade squamous intraepithelial lesions (HSILs), the immediate precursor of cervical cancer, consists largely of surgical treatment for women at higher risk for progression to cancer. The authors' objective was to describe the occurrence of cervical HSIL in the United States and various outcomes for women who received surgical treatment. METHODS: From a US commercial health insurer, a cohort of adult women with cervical HSIL diagnoses receiving surgical treatment within 3 months of diagnosis between January 2008 and September 2018 was identified. This cohort was followed for several outcomes, including cervical HSIL recurrence, human papillomavirus clearance, preterm birth, infection, and bleeding. RESULTS: The incidence rate of cervical HSIL declined from 2.34 (95% CI = 2.30-2.39) cases per 1,000 person-years in 2008 to 1.39 (95% CI = 1.35-1.43) cases per 1,000 person-years in 2014, remaining near that level through 2018. Among 65,527 women with cervical HSIL, 47,067 (72%) received surgical treatment within 3 months of diagnosis. Among the women receiving surgical treatment, cervical HSIL recurred in 6% of surgically treated women, whereas 45% of surgically treated women underwent subsequent virological testing that indicated human papillomavirus clearance. Preterm birth was observed in 5.9% by 5 years follow-up and bleeding and infection each at 2.2% by 7 days follow-up. CONCLUSIONS: From 2008 through 2018, the incidence of diagnosed cervical HSIL decreased for several years before stabilizing. Surgical treatment of HSIL may be beneficial in removing the precancerous lesion, but cervical HSIL may recur, and the surgery is associated with complications including preterm birth, infection, and bleeding.

Attributes underlying patient choice of treatment modality for low-grade squamous intraepithelial lesion complicated by high-risk human papillomavirus infection.

OBJECTIVE: To use logistic regression to analyze the attributes underlying patients' treatment options for low-grade squamous intraepithelial lesion (LSIL) complicated with high-risk human papillomavirus (HR-HPV) infection, and identify the best benefit group of different treatment options. METHODS: Clinical data of 197 LSIL patients with HR-HPV infection between June 2009 and February 2022 were collected. According to the treatment options chosen by the patients, they were divided into the interferon, photodynamic therapy, follow-up observation, and focused ultrasound (FUS) treatment groups. One-way analysis of variance (ANOVA) and multivariate logistic regression analysis were used to analyze the influencing factors, including age, occupation, education level, maternity history, reason for encounter, route of consultation, annual personal and household income, screening for related risk factors, and identifying the best benefit group of different treatment options. RESULTS: One-way ANOVA revealed a statistically significant difference in age, education level, maternity history, reason for encounter, and annual household income (p < 0.05). Multivariate logistic regression analysis was performed on these five factors, indicating that age ≤35 years, high school educational level or higher, and no childbirth history were independent risk factors influencing patients' choices of FUS treatment. The receiver operating characteristic curve was used to determine the age threshold of 31 years. CONCLUSION: Age, educational level, and maternity history were independent risk factors influencing patients' choice of treatment modality for LSIL complicated with HR-HPV infection. Age ≤31 years, high school, equivalent, or higher educational level, and no childbirth yielded a higher rate of choosing FUS treatment for LSIL patients with HR-HPV infection.

Anal Squamous Cell Carcinoma in Ulcerative Colitis: Can Pouches Withstand Traditional Treatment Protocols?

BACKGROUND: Anal squamous cell carcinoma has rarely been reported in the setting of ulcerative colitis. OBJECTIVE: This study aimed to understand the prognosis of anal squamous cell carcinoma in the setting of ulcerative colitis. DESIGN: This is a retrospective review. SETTING: This study was conducted at a referral center. PATIENTS: Adult patients with both ulcerative colitis (556.9/K51.9) and anal squamous cell carcinoma (154.3/C44.520) between January 1, 2000 and August 1, 2019 were included. MAIN OUTCOMES MEASURES: The primary outcomes measured are treatment and survival of anal squamous cell carcinoma. RESULTS: Of the 13,499 patients with ulcerative colitis treated, 17 adult patients with ulcerative colitis and anal dysplasia and/or anal squamous cell carcinoma were included in the study: 6 had a diagnosis of anal squamous cell carcinoma, 8 had high-grade squamous intraepithelial lesions, and 3 had low-grade squamous intraepithelial lesions. There were 4 men (23%) and a median age of 55 years (range, 32-69) years. At diagnosis, 6 had an IPAA, of which 5 had active pouchitis, 1 had an ileorectal anastomosis with active proctitis, 1 had a Hartmann stump with disuse proctitis, 5 had pancolitis, and 4 had left-sided colitis. Of the 6 with anal squamous cell carcinoma, all received 5-fluorouracil and mitomycin C with external beam radiation therapy. Four patients had an IPAA, all of whom required intestinal diversion or pouch excision because of treatment intolerance. At a median follow-up of 60 months, 3 patients died: one at 0 months (treatment-related myocardial infarction), one at 60 months (metastatic anal squamous cell carcinoma), and one at 129 months (malignant peripheral nerve sheath tumor); the remaining patients had no residual disease. LIMITATIONS: This study was limited because of its retrospective nature and small number of patients. CONCLUSION: Anal squamous cell carcinoma in the setting of ulcerative colitis is extremely rare. In the setting of IPAA, diversion may be necessary to prevent radiation intolerance. Careful examination of the perianal region should be performed at the time of surveillance endoscopy. See Video Abstract at http://links.lww.com/DCR/B582. CARCINOMA ANAL DE CLULAS ESCAMOSAS EN COLITIS ULCEROSA PUEDE EL POUCH MODIFICAR LOS RESULTADOS DE LOS PROTOCOLOS DE TRATAMIENTO TRADICIONAL: ANTECEDENTES:La incidencia de cáncer anal de células escamosas es muy baja en pacientes con colitis ulcerosa.OBJETIVO:Comprender el pronóstico del cáncer anal de células escamosas en el contexto de la colitis ulcerosa.DISEÑO:Revisión retrospectiva.AJUSTE:Centro de referencia.PACIENTES:Pacientes adultos con colitis ulcerosa (556.9 / K51.9) y cáncer anal de células escamosas (154.3 / C44.520) entre el 1 de enero de 2000 y el 1 de agosto de 2019.RESULTADOS PRINCIPALES:Tratamiento y sobrevida del cáncer anal de células escamosas.RESULTADOS:De 13.499 pacientes en tratamiento por colitis ulcerosa, diecisiete presentaron displasia y/o cáncer de células escamosas: 6 con cáncer, 8 con lesiones intraepiteliales escamosas con displasia de alto grado y 3 con displasia de bajo grado.Cuatro son hombres (23 %) con una mediana de 55 años (rango 32-69). Al realizar el diagnóstico 6 tenían pouch, 5 con pouchitis activa; 1 con ileorecto anastomosis con proctitis activa y 1 con operación de Hartman y muñón con colitis por desuso; además 5 tenían pancolitis y 4 tenían colitis izquierdaTodos los casos con cáncer anal de células escamosas (6 pacientes), fueron tratados con 5-FU mas Mitomicina y radioterapia externa. Cuatro pacientes tenían pouch, todos requirieron derivación intestinal o escisión del pouch por intolerancia al tratamiento.En la mediana de seguimiento de 60 meses, tres pacientes fallecieron: uno a los 0 meses (infarto de miocardio relacionado con el tratamiento), uno a los 60 meses (cáncer de células escamosas metastásico) y uno a los 129 meses (tumor maligno de la vaina del nervio periférico); el resto no presentaba enfermedad residual.LIMITACIONES:Revisión retrospectiva, número pequeño de pacientes.CONCLUSIÓN:El cáncer anal de células escamosas en el contexto de la colitis ulcerosa es extremadamente raro. En el contexto de IPAA, la derivación puede ser necesaria para prevenir la intolerancia a la radiación. Se debe realizar un examen cuidadoso de la región perianal en el momento de la endoscopia de control. Consulte Video Resumen en http://links.lww.com/DCR/B582.

Risk factors for ≥high-grade anal intraepithelial lesions in MSM living with HIV and the response to topical and surgical treatments.

BACKGROUND: The objective of this study in MSM living with HIV was to determine the incidence of HSIL and ASCC, related factors, and the response to treatment. PATIENTS AND METHODS: Data were gathered in 405 consecutive HIV-infected MSM (May 2010-December 2018) at baseline and annually on: sexual behavior, anal cytology, and HPV PCR and/or high-resolution anoscopy results. They could choose mucosectomy with electric scalpel (from May 2010) or self-administration of 5% imiquimod 3 times weekly for 16 weeks (from November 2013). A multivariate logistic regression model was developed for ≥HSIL-related factors using a step-wise approach to select variables, with a significance level of 0.05 for entry and 0.10 for exit, applying the Hosmer-Lemeshow test to assess the goodness of fit. RESULTS: The study included 405 patients with a mean age of 36.2 years; 56.7% had bachelor´s degree, and 52.8% were smokers. They had a mean of 1 (IQR 1-7) sexual partner in the previous 12 months, median time since HIV diagnosis of 2 years, and mean CD4 nadir of 367.9 cells/uL; 86.7% were receiving ART, the mean CD4 level was 689.6 cells/uL, mean CD4/CD8 ratio was 0.77, and 85.9% of patients were undetectable. Incidence rates were 30.86/1,000 patient-years for ≥high squamous intraepithelial lesion (HSIL) and 81.22/100,000 for anal squamous cell carcinoma (ASCC). The ≥HSIL incidence significantly decreased from 42.9% (9/21) in 2010 to 4.1% (10/254) in 2018 (p = 0.034). ≥HSIL risk factors were infection with HPV 11 (OR 3.81; 95%CI 1.76-8.24), HPV 16 (OR 2.69, 95%CI 1.22-5.99), HPV 18 (OR 2.73, 95%CI 1.01-7.36), HPV 53 (OR 2.97, 95%CI 1.002-8.79); HPV 61 (OR 11.88, 95%CI 3.67-38.53); HPV 68 (OR 2.44, CI 95% 1.03-5.8); low CD4 nadir (OR1.002; 95%CI 1-1.004) and history of AIDS (OR 2.373, CI 95% 1.009-5.577). Among HSIL-positive patients, the response rate was higher after imiquimod than after surgical excision (96.7% vs 73.3%, p = 0.009) and there were fewer re-treatments (2.7% vs 23.4%, p = 0.02) and adverse events (2.7% vs 100%, p = 0.046); none developed ASCC. CONCLUSIONS: HSIL screening and treatment programs reduce the incidence of HSIL, which is related to chronic HPV infection and poor immunological status. Self-administration of 5% imiquimod as first-line treatment of HSIL is more effective than surgery in HIV+ MSM.

Anogenital High-Grade Squamous Intraepithelial Lesion Comorbid With Vulvar Lichen Sclerosus and Lichen Planus.

OBJECTIVE: The aim of the study was to describe the clinicopathologic features of vulvovaginal or anal high-grade squamous intraepithelial lesion (HSIL) comorbid with lichen sclerosus and/or lichen planus (LS/LP). METHODS: The local pathology database identified 37 consecutive cases from 2007 to 2019 of vulvar, vaginal, or anal HSIL among women who had a histopathologic diagnosis of vulvar LS/LP. Cases had p16 and p53 immunoperoxidase stains. Clinical data included age, relative location of HSIL and LS/LP, immune-modifying conditions, tobacco use, treatment type, and follow-up. Histopathologic data included HSIL morphology categorized as warty-basaloid or keratinizing, p16 and p53 patterns within HSIL, and features of LS/LP. RESULTS: The mean age was 69 years with a median follow-up up 42 months. Lichen sclerosus, alone or in combination with LP, was the comorbid dermatosis in 89%. Lichen sclerosus/lichen planus was overlapping or adjacent to HSIL in two-thirds of cases and located separately in the remainder. Rates of tobacco use and immunologic dysfunction were each 40%. In cases of co-located LS and HSIL, sclerosis was absent under the neoplasia in 57%. Twenty-four percent of HSIL cases showed keratinizing morphology; block-positive p16 and suprabasilar-dominant p53 helped distinguish HSIL from human papillomavirus-independent neoplasia. CONCLUSIONS: Histopathologic identification of comorbid HSIL and LS/LP may be challenging because of keratinizing morphology and loss of diagnostic features of LS. Clinicopathologic correlation and use of p16 and p53 are essential to achieve an accurate diagnosis and enact disease-specific management plans.

The Conundrum of an Accumulating Acuminatum.

BACKGROUND A 70-year-old African American man presented with fatigue, dizziness, generalized weakness, and considerable weight loss of over 20 pounds in 3 weeks. History-taking revealed he was positive for HIV, hepatitis C, and severe chronic condyloma acuminatum, which had been progressing for 16 years. Treatment and surgical intervention had been continuously postponed due to the patient's long-standing history of heroin abuse. CASE REPORT Physical exam and diagnostics showed evidence of sepsis. He was hypotensive, with lactic acidosis and significant leucocytosis, and had acute-on-chronic kidney disease. Urinalysis was positive for nitrites and leukocyte esterase; therefore, broad-spectrum antibiotics were initiated. Additional sources of sepsis were considered due to persistent leucocytosis despite appropriate antibiotic coverage. An MRI of the pelvis was done to evaluate for necrosis of fistulization from potential internal warts as a source of sepsis. The lesions extended from the inguinal areas bilaterally, covering the medial thighs, lower scrotal wall, and wall junction. It had infiltrated the perineum and the entire rectal area, including the gluteal cleft and anus. The patient was consulted by colorectal surgery, urology, and infectious disease services. CONCLUSIONS Surgical biopsies found that he had both low- and high-grade squamous intraepithelial neoplasia. There was no evidence of invasive carcinoma, which was a concern given his weight loss. Surgery devised a plan that included a diverting colostomy (allowing the infected anal area to heal), followed by resection of his giant condyloma, and re-anastomosing of the bowels to return him to a normal baseline anatomy. A favorable prognosis was expected.

Brief Report: Recurrence of Anal High-Grade Squamous Intraepithelial Lesions Among Women Living With HIV.

BACKGROUND: Women living with HIV (WLHIV) have a high risk of developing invasive anal cancer. Anal cancer may be prevented with early detection and treatment of anal histologic high-grade squamous intraepithelial lesions (HSIL). However, there are limited data on the efficacy of anal HSIL treatment in WLHIV. STUDY DESIGN: We conducted a retrospective study of WLHIV treated for anal HSIL under high-resolution anoscopy (HRA) guidance from January 1, 2007 to December 31, 2017 with at least one post-treatment visit at an urban tertiary care hospital. RESULTS: Forty-five WLHIV women with at least 1 follow-up evaluation after treatment for anal HSIL were identified. The median age was 46 years (range 35-66 years), 63% were African American, 27% were Hispanic/Latino, and 53% were current smokers. The mean absolute CD4 T-cell count was 516 cells/mm; 50% and 24% of the cohort had a history of cervical or vulvar HSIL respectively. The cumulative probability of anal HSIL recurrence was 29% at 12 months, 52% at 24 months, and 79% at 36 months post-treatment. CONCLUSION: Most WLHIV treated for anal HSIL recurred within 3 years, suggesting need for continued surveillance after treatment. Our data contribute to the information needed to develop effective anal cancer prevention guidelines in WLHIV.

Association of Bacterial Vaginosis and Human Papilloma Virus Infection With Cervical Squamous Intraepithelial Lesions.

OBJECTIVES: Human papillomavirus (HPV) is known to be associated with squamous intraepithelial lesions (SILs). However, there is limited and conflicting literature on the relationship between bacterial vaginosis (BV) and SIL. The aim of this study is to determine the prevalence of BV and evaluate the association between BV and SIL. METHODS: A retrospective study was performed on 10,546 cases between 2012 and 2017. HPV results were available in 7,081 cases. RESULTS: BV was present in 17.6% of cases. There was significant association between BV, positive HPV infection, and high-grade SIL. BV patients with negative HPV infection showed more squamous abnormalities than BV-negative HPV-negative patients. CONCLUSIONS: We found there is a significant association between BV and SIL. BV is more common among patients with HPV infection and is independently associated with squamous abnormalities in cervical smears and surgical follow-up.

Association of anal symptoms with anal high grade squamous intraepithelial lesions (HSIL) among men who have sex with men: Baseline data from the study of the prevention of anal cancer (SPANC).

BACKGROUND: The association between anal high-grade squamous intraepithelial lesion (HSIL) and anal symptoms has not been systematically investigated. METHODS: The Study of Prevention of Anal Cancer is a prospective cohort study of men who have sex with men (MSM) ≥ 35 years old in Sydney, Australia. Self-reported symptoms were collected. Anal cytology and high-resolution anoscopy were undertaken. Using baseline visit data, men negative for squamous intra-epithelial lesion (SIL) were compared with men diagnosed with composite-HSIL (cytology and/or histology). Logistic regression analyses were performed to assess the association of symptoms with HSIL. RESULTS: Among 414 MSM included (composite-HSIL (n = 231); negative for SIL (n = 183)), 306 (73.9%) reported symptom(s) within the last 6 months. There was no association between any symptom and composite-HSIL. A significant association between anal lump and a larger burden of HSIL (at least 2 intra-anal octants) (anal lump within last month: p = 0.014; anal lump within last 6 months: p = 0.010) became non-significant after adjusting for HIV-status and recent anal warts (anal lump within last month: p = 0.057; anal lump within last 6 months: p = 0.182). CONCLUSIONS: Among MSM age 35 years and older, most anal symptoms are not a useful marker of anal HSIL.