Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.

BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

Feasibility study of focused ultrasound in the treatment of vulvar low-grade squamous intraepithelial lesions with persistent symptoms.

OBJECTIVE: This study aimed to investigate the feasibility, efficacy, and safety of focused ultrasound (FUS) for the treatment of vulvar low-grade squamous intraepithelial lesions (VLSIL) with persistent symptoms. METHODS: This retrospective analysis included 24 VLSIL patients who underwent FUS treatment. At each follow-up visit, the clinical response was assessed including changes in symptoms and signs. In addition, the histological response was assessed based on the vulvar biopsy results of the 3rd follow-up. Clinical and histological response were assessed to elucidate the efficacy. RESULTS: A total of 22 patients completed follow-up and post-treatment pathological biopsies. After treatment, the clinical scores of itching decreased from 2.55 ± 0.51 to 0.77 ± 0.81 (p < 0.05). Furthermore, the clinical response rate and histological response rate were 86.4% and 81.8%, respectively. Only two cured patients indicated recurrence in the 3rd and 4th year during the follow-up period and achieved cure after re-treatment. In terms of adverse effects, only one patient developed ulcers after treatment, which healed after symptomatic anti-inflammatory treatment without scarring, and no other treatment complications were found in any patients. None of the patients developed a malignant transformation during the follow-up period. CONCLUSION: This study revealed that FUS is feasible, effective, and safe for treating VLSIL patients with persistent symptoms, providing a new solution for the noninvasive treatment of symptomatic VLSIL.

Immunotherapy in patients with local HPV infection and high-grade squamous intraepithelial lesion following uterine cervical conization.

OBJECTIVE: To establish the clearance of cervical human papillomavirus (HPV) infection following postoperative immunotherapy with inosine pranobex in women receiving surgical treatment of established high-grade squamous intraepithelial lesion (HSIL) of the uterine cervix. MATERIALS AND METHODS: Over the six-year study period, 32 women with cervical HPV infection following electroconization (loop electrosurgical excision procedure) of the uterine cervix for established HSIL were randomly divided into two groups: I (n = 10) without and II (n = 22) with postoperative inosine pranobex immunotherapy. Follow-up after 24 and 48 months included cervical testing for HPV persistence and after 12, 24, and 48 months with cytology and colposcopy for dysplasia relapse (confirmed histologically). RESULTS: Relapse monitoring in 32 women after 12 months revealed 1 and 0 HSIL positive in groups I and II, respectively; after 24 months an additional 3 patients in each group were positive; and after 48 months an additional 3 and 1 patients were positive in groups I and II, respectively (p < .05). The groups significantly differed (p < .05) with regard to clearing the most common high-risk HPV genotypes (HPV 16 and HPV 56). CONCLUSIONS: Inosine pranobex immunotherapy in HPV-positive patients following cervical conization significantly increased the clearance of viral infection with high-risk genotypes and reduced relapse of HSIL.

Anal squamous intraepithelial lesions: an update and proposed management algorithm.

The term anal squamous intraepithelial lesion (ASIL) is used to describe premalignant change of anal squamous cells that precede the development of squamous cell carcinoma. Pathophysiology is driven by the human papilloma virus (HPV), and progression and regression of ASIL being well described, with 12% of high-grade lesions progressing to invasive cancer within 5 years. Vaccination against HPV is effective for primary prevention. Management consists of identification and treatment of high-grade lesions to prevent progression to squamous cell carcinoma. Management of established ASIL aims to avoid the progression to invasive cancer and maintain fecal continence. A combination of surveillance, excision, ablative, or topical therapies is used to achieve this. The aim of the present study was to review the contemporary evidence about ASIL and to suggest a management algorithm.

Short-term effectiveness and tolerability of carbon dioxide laser for anal high-grade squamous intraepithelial lesions in individuals living with HIV.

BACKGROUND: Ablative treatment of intra-anal high-grade squamous intraepithelial lesions (HSIL) reduces the risk of progression to anal squamous cell carcinoma. Our objective was to assess the short-term effectiveness and tolerability of the carbon dioxide laser for treating intra-anal HSIL in patients at high risk of anal cancer. METHODS: This is an exploratory, pilot, single-arm, clinical trial of treatment response for anal HSIL in people living with HIV diagnosed with ≤3 not previously treated HSILs. Individuals were treated with one carbon dioxide laser treatment session. Clinical assessment by high resolution anoscopy and systematic recording of adverse events was performed. RESULTS: Fifty-two patients with 72 HSILs were included. Response to treatment was assessed in 48 (92.3%) patients; in the per-protocol population analysis, complete, partial, and no response was seen in 50% (n = 24), 20.8% (n = 10) and 29.1% (n = 14), respectively. Being older than 40 years and having a CD4 T-cell count lower than 200 cells/µL at diagnosis of HSIL were significantly associated with a poor response to treatment. Data on adverse events was recorded for 49 patients and 69.4% (n=34) reported no symptoms after the procedure. CONCLUSIONS: Carbon dioxide laser ablation is a promising and well tolerated treatment for intra-anal HSIL.

Cervical cancer screening coverage, management of squamous intraepithelial lesions and related costs in France.

Until 2018, cervical cancer screening in France was an unorganized individual screening, with the exception of some pilot programs in some territories. We aimed to assess, before the implementation of organized cervical cancer screening and human papillomavirus (HPV) nonavalent vaccine introduction in the vaccination schedule in 2018, (i) the individual cervical cancer screening coverage, (ii) the management of squamous intraepithelial lesions (SIL) and (iii) the related costs. We used the Système National des Données de Santé (SNDS) (Echantillon Généraliste de Bénéficiaires [EGB] and Programme de Médicalisation des systèmes d'information [PMSI]) to assess the cervical screening coverage rate in France between January 1st, 2012 and December 31st, 2014, and to describe diagnostic investigations and therapeutic management of SIL in 2013. After extrapolation to the general population, a total of 10,847,814 women underwent at least one smear test over the 3-year study period, corresponding to a coverage rate of 52.4% of the women aged 25 to 64 included. In 2013, 126,095 women underwent HPV test, 327,444 women underwent colposcopy, and 9,653 underwent endocervical curettage; 31,863 had conization and 12,162 had laser ablation. Besides, 34,067 women experienced hospital stays related to management of SIL; 25,368 (74.5%) had high-grade lesions (HSIL) and 7,388 (21.7%) low-grade lesions (LSIL). Conization was the most frequent in-hospital therapeutic procedure: 89.5% (22,704) of women with an in-hospital procedure for HSIL and 64.7% (4,781) for LSIL. Mean cost of smear test, colposcopy and HPV tests were around 50€. Total cost for hospital stays in 2013 was estimated at M41€, or a mean cost of 1,211€ per woman; 76% were due to stays with HSIL. This study highlights the low coverage rate of individual cervical cancer screening and a high burden related to SIL management.

Manifestaciones clínicas y anoscópicas de las lesiones ecamosas intraepiteliales de alto grado anales / Clinical and anoscopic manifestations of high-grade anal squamous intraepithelial lesions

Introducción: Las lesiones escamosas intraepiteliales de alto grado anales (H-ASIL) son consideradas el precursor del carcinoma escamoso anal. Es por esto que distintas Sociedades recomiendan su pesquisa y tratamiento en poblaciones de alto riesgo. El objetivo del trabajo es describir las manifestaciones de H-ASIL en la anoscopía de alta resolución (AAR) en nuestros pacientes. Diseño: Retrospectivo, descriptivo. Pacientes y métodos: Revisión de historias clínicas e imágenes de AAR de pacientes con diagnóstico de H-ASIL entre enero de 2016 y julio de 2017. La evaluación anoscópica incluyó la unión escamocolumnar, el conducto anal distal y el área perianal. Frente al hallazgo de una lesión sospechosa de ASIL, se tomaron biopsias. Resultados: Entre enero de 2016 y julio de 2017 se realizaron 184 AAR. Se biopsiaron 143 lesiones sospechosas de ASIL. Veintiséis de ellas, presentes en 13 pacientes fueron H-ASIL. Once hombres (diez hombres que tienen sexo con hombre (HSH) con infección por VIH). Todas las lesiones eran subclínicas y se encontraron a nivel endoanal; eran en su totalidad acetoblancas. Se buscaron áreas con puntillado y/o mosaico sugestivas de ASIL. El uso de Lugol nos permitió aumentar el grado de sospecha y delimitar las lesiones. Se tomaron biopsias para anatomía patológica bajo visión directa. Conclusiones: Las H-ASIL son consideradas en la actualidad las precursoras del carcinoma escamoso anal; su detección y tratamiento prevendrían su desarrollo. En nuestra casuística, todos los pacientes se encontraban en al menos un grupo de riesgo. Las lesiones fueron subclínicas y requirieron de la anoscopía de alta resolución para su hallazgo, lo que permitió realizar un tratamiento dirigido. Es importante que los profesionales de la salud consideren la pesquisa de H-ASIL en población de riesgo. (AU)

Introduction: The high-grade anal intraepithelial lesions (H-ASIL) are considered the precursor of the anal squamous cell carcinoma. This is why different societies recommend the screening and treatment in high-risk populations. The objective of this paper is to describe H-ASIL manifestations in the high resolution anoscopy (HRA) in our patients. Design: Retrospective, Descriptive Patients and Methods: Review of clinical histories and pictures of HRA of patients with H-ASIL diagnosis between January 2016 and July 2017. The anoscopic evaluation included the squamocolumnar junction, the distal anal duct and the perianal area. In case of the finding of a suspicious lesion of ASIL, biopsies were taken. Results: Between January 2016 and July 2017 184 HRA were performed. 143 ASIL suspicious lesion were biopsied. Twentysix of them, in 13 patients, were H-ASIL. Eleven were men (10 men who have sex with men with HIV infection). All lesions were subclinical and found at endoanal level. The totality of them were acetowhite. Areas with coarse punctation and a mosaic pattern were suggestive of ASIL. The use of lugol´s iodine allows us to increase the grade of suspect and delimit the lesions. Biopsies were taken for pathology under direct vision. Conclusion: The H-ASIL are considered at the present the precursors of the anal squamous carcinoma. Its development could be prevented with de proper detection and treatment of the H-ASIL. In our casuistic, all patients are in at least one risk group. The lesions were subclinical and required of the high resolution anoscopy for their finding, which allows to perform a directed treatment. It is important that health professionals consider the H-ASIL screening in risk population. (AU)