RESUMEN
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.).
Asunto(s)
Neoplasias del Ano , Infecciones por VIH , Lesiones Precancerosas , Lesiones Intraepiteliales Escamosas , Espera Vigilante , Adulto , Neoplasias del Ano/etiología , Neoplasias del Ano/patología , Neoplasias del Ano/prevención & control , Neoplasias del Ano/terapia , Biopsia , Femenino , Infecciones por VIH/complicaciones , Homosexualidad Masculina , Humanos , Masculino , Infecciones por Papillomavirus/complicaciones , Lesiones Precancerosas/etiología , Lesiones Precancerosas/patología , Lesiones Precancerosas/terapia , Estudios Prospectivos , Lesiones Intraepiteliales Escamosas/etiología , Lesiones Intraepiteliales Escamosas/patología , Lesiones Intraepiteliales Escamosas/terapiaRESUMEN
BACKGROUND: International data on anogenital HPV infection incidence among men are limited. METHODS: Incidence of incident-persistent (IP) anogenital HPV infections was evaluated among 295 men who have sex with men (MSM) and 1576 heterosexual men (HM) aged 16-27 years in the placebo arm of a global, multicenter 4-valent (4v) HPV vaccine trial. We estimated IP incidence (penile/scrotal, perineal/perianal, anal) for 4vHPV and 9-valent (9v) HPV vaccine types and cumulative IP incidence over 36 months. RESULTS: IP infection incidence per 100 person-years (95% CI) among HM for 4vHPV and 9vHPV types was 4.1 (3.5-4.9) and 6.8 (5.9-7.6) at penile/scrotal, and 1.2 (.8-1.6) and 1.9 (1.5-2.4) at perineal/perianal sites, respectively; and among MSM, IP infection incidence was 2.3 (1.3-3.8) and 3.2 (2.0-4.9) at penile/scrotal, 6.8 (4.9-9.2) and 9.0 (6.9-11.6) at perineal/perianal, and 12.0 (9.4-15.1) and 16.8 (13.7-20.2) at anal sites, respectively. Cumulative IP incidence over 36 months (excluding anal canal; any 9vHPV type) was higher among MSM versus HM (24.1% vs 18.4%). CONCLUSIONS: A substantial proportion of unvaccinated men of catch-up vaccination age developed IP 9vHPV-related infections. Gender-neutral vaccination could decrease male HPV infection, contribute to herd protection, and reduce disease burden. Clinical Trials Registration. NCT00090285.
Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Minorías Sexuales y de Género , Humanos , Masculino , Homosexualidad Masculina , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , PapillomaviridaeRESUMEN
The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post-transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision-making, provided there is adequate capacity to perform diagnostic procedures (high-resolution anoscopy [HRA]). Anal cytology, high-risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV-cytology co-testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow-up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk-targeted screening for anal cancer prevention.
Asunto(s)
Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Homosexualidad Masculina , Detección Precoz del Cáncer , Papillomavirus Humano 16 , PapillomaviridaeRESUMEN
BACKGROUND: Targeted ablation of anal canal high-grade dysplasia results in high recurrence over time. Circumferential radiofrequency ablation might decrease recurrence. OBJECTIVE: This study aimed to determine the safety and efficacy of circumferential radiofrequency ablation for anal high-grade dysplasia. DESIGN: This was a dual-center, prospective trial of circumferential radiofrequency ablation with a 1-year follow-up with longer follow-up data abstracted from medical records of study patients returning after trial for surveillance. Ten participants from the identically conducted pilot circumferential radiofrequency ablation trial were included to improve sample size for longer-term analysis. SETTINGS: This study included 3 surgeons at 2 sites. PATIENTS: The study included 51 patients undergoing circumferential radiofrequency ablation for anal canal high-grade dysplasia. INTERVENTION: Circumferential radiofrequency ablation of anal canal high-grade dysplasia and targeted radiofrequency ablation of recurrence. MAIN OUTCOME MEASURES: The primary outcome measures were circumferential radiofrequency ablation efficacy and associated morbidity. RESULTS: Fifty-one participants underwent circumferential radiofrequency ablation but 48 participants returned for 1 or more postprocedure high-resolution anoscopy and were evaluable. The mean age of participants was 43 years, most were male (94%), 33% were living with HIV, and 58% had 3 or more high-grade dysplasias treated. Sixty percent had no recurrence, whereas 19% had 1 recurrence, 15% had 2 recurrences, and 6% had 3 recurrences. Most recurrences (66%) developed within the first 6 months. Kaplan-Meier probability of recurrence combining both series was 19% at 3 months, 30% at 6 months, and approximately 40% after 6 months out to 30 months. Most common morbidities were pain (85.4%) lasting for a median of 21 (range, 4-91) days and bleeding (91%) lasting for a median of 21 (range, 5-87) days. Of those with pain and bleeding, 65% and 85%, respectively, described it as mild. No patients developed fistulas, stricture, or incontinence. No serious adverse events related to circumferential radiofrequency ablation occurred. Having a previous recurrence was the only significant predictor of a subsequent recurrence (HR, 28.53) for recurrence at 9 months or before. LIMITATIONS: Enrollment ended prematurely, 10 participants from the pilot study were combined to increase the sample size, and longer-term follow-up was collected retrospectively were the limitations of this study. CONCLUSIONS: Circumferential radiofrequency ablation has improved efficacy over targeted ablation but with increased pain and bleeding. See Video Abstract at http://links.lww.com/DCR/B973 . ESTUDIO PROSPECTIVO BICNTRICO SOBRE LA ABLACIN POR RADIOFRECUENCIA CIRCUNFERENCIAL DE LESIONES ANALES INTRAEPITELIALES ESCAMOSAS DE ALTO GRADO DEMOSTRANDO MAYOR EFICACIA A LARGO PLAZO CON RELACIN A CONTROLES HISTRICOS DE ABLACIN DIRIGIDA: ANTECEDENTES:La ablación dirigida de la displasia de alto grado en el canal anal proporciona como resultados una alta recidiva a largo plazo. La ablación por radiofrecuencia circunferencial podría disminuir la reincidencia.OBJETIVO:Determinar la seguridad y eficacia de la ablación por radiofrecuencia circunferencial para la displasia anal de alto grado.DISEÑO:Estudio prospectivo bicéntrico de ablación por radiofrecuencia circunferencial con un seguimiento de 1 año, en base al monitoreo prolongado de datos, obtenidos de los registros medicos, de todos los pacientes incluidos en el estudio y que fueron controlados clinicamente. Diez participantes del estudio piloto de ablación por radiofrecuencia circunferencial realizada de manera idéntica, se combinaron para mejorar el análisis del tamaño de la muestra a largo plazo.PACIENTES:Se incluyeron 51 pacientes sometidos a la ablación por radiofrecuencia circunferencial de una lesion displásica de alto grado en el canal anal.AJUSTES:Tres cirujanos en 2 centros.INTERVENCIÓN:Ablación por radiofrecuencia circunferencial de la displasia de alto grado en el canal anal y ablación por radiofrecuencia dirigida de la recidiva.PRINCIPALES MEDIDAS DE RESULTADOS:Las medidas primarias fueron la eficacia de la ablación por radiofrecuencia circunferencial y la morbilidad asociada.RESULTADOS:Cincuenta y un participantes se sometieron a la ablación por radiofrecuencia circunferencial, de los cuales, 48 regresaron para ser evaluados con ≥1 anuscopias de alta resolución, después del procedimiento. La edad media de los participantes fue de 43 años, en su mayoría hombres (94%), el 33% eran portadores de VIH y el 58% tenía ≥3 lesiones displásicas de alto grado tratadas. El sesenta por ciento no tuvo recidiva, mientras que el 19%, 15% y 6% tuvieron 1, 2 o 3 recidivas. La mayoría de las recaídas (66%) se desarrollaron dentro de los primeros 6 meses. La probabilidad de recurrencia de Kaplan-Meier combinando ambas series fue del 19 % a los 3 meses, del 30 % a los 6 meses y aproximadamente del 40 % entre los 6 y 30 meses. Los indicadores de morbilidad más frecuentes fueron, el dolor (85,4%) con una mediana de duración de 21 días (rango, 4-91) y sangrado (91%) con una mediana de duración de 21días (rango, 5-87). Aquellos pacientes con dolor (65%) y sangrado (85%) respectivamente, los describieron como leves. Ningún paciente desarrolló fístula, estenosis o incontinencia. No se produjeron eventos adversos graves relacionados con la ablación por radiofrecuencia circunferencial. Tener una recurrencia previa fue el único factor predictivo importante de una recidiva ulterior (RH 28,53) en casos de recaída a los 9 meses o antes.LIMITACIONES:Como el registro finalizó prematuramente, se agregaron 10 participantes del estudio piloto para aumentar el tamaño de la muestra. El seguimiento a largo plazo fué recopilado retrospectivamente.CONCLUSIONES:La ablación por radiofrecuencia circunferencial ha mejorado la eficacia sobre la ablación dirigida pero con dolor y sangrado mas importantes. Consulte Video Resumen en http://links.lww.com/DCR/B973 . ( Traducción-Dr. Xavier Delgadillo ).
Asunto(s)
Lesiones Precancerosas , Ablación por Radiofrecuencia , Lesiones Intraepiteliales Escamosas , Humanos , Masculino , Adulto , Femenino , Canal Anal/patología , Lesiones Precancerosas/patología , Estudios Retrospectivos , Estudios Prospectivos , Proyectos Piloto , Lesiones Intraepiteliales Escamosas/patología , DolorRESUMEN
BACKGROUND: In men, the incidence of human papillomavirus (HPV)-related cancer is rising, but data regarding male HPV infection and seroprevalence are available from only a few countries. METHODS: This analysis of a global HPV vaccine trial evaluated baseline data from 1399 human immunodeficiency virus-negative heterosexual men (HM) and men who have sex with men (MSM). Key objectives included assessment of HPV prevalence and risk factors for seropositivity to 9-valent HPV (9vHPV) vaccine types (6, 11, 16, 18, 31, 33, 45, 52, and 58), and concordance between seropositivity and prevalent HPV type. RESULTS: Overall, 455 of 3463 HM (13.1%) and 228 of 602 MSM (37.9%) were HPV DNA positive for any 9vHPV vaccine type at baseline. Infection prevalence and seroprevalence (≥1 9vHPV vaccine type) were 13.2% and 8.1%, respectively, among 333 HM from Europe, and 37.9% and 29.9%, respectively, among 335 MSM from Europe or North America. Among men with baseline infection, MSM had higher seroprevalence for concordant HPV types (39.5% vs 10.8% in HM). The seropositivity risk (irrespective of baseline infection status) was higher among MSM versus HM (age-adjusted odds ratio, 3.0 [95% confidence interval, 2.4-6.4]). Among MSM, statistically significant seropositivity risk factors included younger age at sexual debut, higher number of receptive anal sex partners, and less frequent condom use. No factors assessed were associated with seropositivity in HM. CONCLUSIONS: Higher proportions of MSM than HM were HPV DNA positive and seropositive, and concordance between HPV DNA positivity and seropositivity, a potential marker of true infection versus carriage, was higher in MSM. Most MSM and HM were seronegative for all 9vHPV vaccine types, suggesting the potential benefit of catch-up vaccination after sexual debut.Clinical Trials Registration. NCT00090285.
Asunto(s)
Alphapapillomavirus , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Homosexualidad Masculina , Humanos , Masculino , Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Prevalencia , Factores de Riesgo , Estudios SeroepidemiológicosRESUMEN
BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. METHODS: Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. RESULTS: Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. CONCLUSIONS: 18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.
Asunto(s)
Alphapapillomavirus , Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Minorías Sexuales y de Género , Lesiones Intraepiteliales Escamosas , Adolescente , Adulto , Canal Anal , Neoplasias del Ano/epidemiología , Neoplasias del Ano/prevención & control , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Prevalencia , Conducta Sexual , Vacunación , Adulto JovenRESUMEN
BACKGROUND: Women living with human immunodeficiency virus (WLHIV) have disproportionately high rates of squamous cell carcinoma of the anus compared with the general population of women. Anal high-grade squamous intraepithelial lesions (HSILs) precede anal cancer, and accurate studies of HSIL prevalence among WLHIV in the United States are lacking. METHODS: The AIDS Malignancy Consortium 084 study was a multicenter national trial to evaluate the prevalence of and risk factors for anal HSIL in a US cohort. Eligible participants were WLHIV aged ≥18 years with no history of anal HSIL. Study participants had an examination including collection of cervical/vaginal and anal specimens, followed by high-resolution anoscopy with biopsy. RESULTS: We enrolled 256 women with evaluable anal pathology. The mean age was 49.4 years, 64% women were non-Hispanic black, 67% were former or current smokers, and 56% reported ever having anal sex with a man. The median CD4 T-cell count was 664 cells/µL. The prevalence of anal histologic HSIL (hHSIL) was 27% (95% confidence interval [CI], 22%-33%). There was a strong concordance (240/254) between local and consensus pathologists for hHSIL vs less than hHSIL (κ = 0.86 [95% CI, .79-.93]). Current CD4 count of ≤200 cells/µL was the strongest predictor of consensus anal hHSIL diagnosis (adjusted odds ratio [aOR], 10.34 [95% CI, 3.47-30.87]). History of anoreceptive intercourse was also associated with hHSIL (aOR, 2.44 [95% CI, 1.22-4.76]). CONCLUSIONS: The prevalence of anal hHSIL in WLHIV in the United States was 27% in this study where all participants received high-resolution anoscopy and biopsy.
Asunto(s)
Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Canal Anal , Neoplasias del Ano/epidemiología , Femenino , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Prevalencia , Factores de Riesgo , Lesiones Intraepiteliales EscamosasRESUMEN
BACKGROUND: Anal high-grade squamous intraepithelial lesions (HSILs) ablation may reduce the incidence of invasive cancer, but few data exist on treatment efficacy and natural regression without treatment. METHODS: An open-label, randomized, multisite clinical trial of human immunodeficiency virus (HIV)-infected adults aged ≥27 years with 1-3 biopsy-proven anal HSILs (index HSILs) without prior history of HSIL treatment with infrared coagulation (IRC). Participants were randomized 1:1 to HSIL ablation with IRC (treatment) or no treatment (active monitoring [AM]). Participants were followed every 3 months with high-resolution anoscopy. Treatment participants underwent anal biopsies of suspected new or recurrent HSILs. The AM participants underwent biopsies only at month 12. The primary end point was complete clearance of index HSIL at month 12. RESULTS: We randomized 120 participants. Complete index HSIL clearance occurred more frequently in the treatment group than in the AM (62% vs 30%; risk difference, 32%; 95% confidence interval [CI], 13%-48%; P < .001). Complete or partial clearance (clearance of ≥1 index HSIL) occurred more commonly in the treatment group (82% vs 47%; risk difference, 35%; 95% CI, 16%-50%; P < .001). Having a single index lesion, compared with having 2-3 lesions, was significantly associated with complete clearance (relative risk, 1.96; 95% CI, 1.22-3.10). The most common adverse events related to treatment were mild or moderate anal pain and bleeding. No serious adverse events were deemed related to treatment or study participation. CONCLUSION: IRC ablation of anal HSILs results in more clearance of HSILs than observation alone.
Asunto(s)
Técnicas de Ablación/métodos , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/cirugía , Hipertermia Inducida/métodos , Lesiones Intraepiteliales Escamosas/diagnóstico , Lesiones Intraepiteliales Escamosas/cirugía , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proctoscopía , Resultado del TratamientoRESUMEN
BACKGROUND: The progression rate and predictors of anal dysplastic lesions to squamous cell carcinoma of the anus remain unclear. Characterizing these parameters may help refine anal cancer screening guidelines. OBJECTIVE: This study aimed to determine the rate of progression of high-grade anal dysplasia to invasive carcinoma in HIV-infected persons. DESIGN: Using the Surveillance, Epidemiology, and End Results database linked to Medicare claims from 2000 to 2011, we identified HIV-infected subjects with incident anal intraepithelial neoplasia III. To estimate the rate of progression of anal intraepithelial neoplasia III to invasive cancer, we calculated the cumulative incidence of anal cancer in this cohort. We then fitted Poisson models to evaluate the potential risk factors for incident anal cancer. SETTINGS: This is a population-based study. PATIENTS: Included were 592 HIV-infected subjects with incident anal intraepithelial neoplasia III. MAIN OUTCOME MEASURES: The primary outcome measured was incident squamous cell carcinoma of the anus. RESULTS: Study subjects were largely male (95%) with a median age of 45.7 years. Within the median follow-up period of 69 months, 33 subjects progressed to anal cancer. The incidence of anal cancer was 1.2% (95% CI, 0.7%-2.5%) and 5.7% (95% CI, 4.0%-8.1%) at 1 and 5 years, following a diagnosis of anal intraepithelial neoplasia III. Risk of progression did not differ by anal intraepithelial neoplasia III treatment status. On unadjusted analysis, black race (p = 0.02) and a history of anogenital condylomata (p = 0.03) were associated with an increased risk of anal cancer incidence, whereas prior anal cytology screening was associated with a decreased risk (p = 0.04). LIMITATIONS: The identification of some incident cancer episodes used surrogate measures. CONCLUSIONS: In our population-based cohort of HIV-infected subjects with long-term follow-up, the risk of progression from anal intraepithelial neoplasia III to anal squamous cell carcinoma was higher than reported in other studies and was not associated with the receipt of anal intraepithelial neoplasia III treatment. See Video Abstract at http://links.lww.com/DCR/A933.
Asunto(s)
Canal Anal/patología , Neoplasias del Ano/etiología , Infecciones por VIH/complicaciones , VIH , Vigilancia de la Población/métodos , Lesiones Precancerosas/patología , Programa de VERF , Adulto , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/epidemiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: More than 90% of anal cancers are caused by human papillomavirus, and human papillomavirus strains 16 and 18 are the most oncogenic. Anal high-grade squamous intraepithelial lesions are cancer precursors. Treating these high-grade intraepithelial lesions likely reduces the risk of cancer, but cytology is an imperfect screening test. OBJECTIVE: The purpose of this study was to determine whether human papillomavirus 16 and/or 18 testing better predicts the presence of high-grade squamous intraepithelial lesions. DESIGN: In this retrospective study, 894 consecutive patients underwent anal dysplasia screening with digital anorectal examination, anal cytology, high-risk human papillomavirus testing, and high-resolution anoscopy with biopsy. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of each test and for a novel screening protocol. The absolute and relative risk of high-grade squamous intraepithelial lesions for all of the cytology/human papillomavirus combinations were also calculated. SETTINGS: The study was conducted at a single practice specializing in anal dysplasia. PATIENTS: Ninety-two percent of participants were men who have sex with men. Forty-four percent were HIV-positive individuals who were well controlled on antiretroviral therapy. The median age was 50 years. MAIN OUTCOME MEASURES: The presence of high-grade squamous intraepithelial lesions as a function of human papillomavirus and the cytology results were measured. RESULTS: High-risk human papillomavirus testing alone demonstrated better sensitivity (96% vs 89%; p = 0.03) and negative predictive value (99% vs 96%; p = 0.008) over cytology. Human papillomavirus 16/18 testing increased specificity (48% to 71%; p < 0.0001) and positive predictive value (24% to 37%; p = 0.003) over testing for all of the high-risk strains. For each cytology category, high-grade squamous intraepithelial lesions were more prevalent when human papillomavirus 16/18 was detected. Benign cytology with 16/18 had a 31-fold increased risk of high-grade squamous intraepithelial lesions. LIMITATIONS: This study was conducted in a single private practice specializing in anal dysplasia screening with a mostly male population, and results might not be generalizable. CONCLUSIONS: Testing of high-risk human papillomavirus strains 16/18 improves specificity and positive predictive value over cytology for anal dysplasia screening. Patients testing positive for strains 16/18 are at a high risk for high-grade squamous intraepithelial lesions and should undergo high-resolution anoscopy regardless of the cytology result. See Video Abstract at http://links.lww.com/DCR/A654.
Asunto(s)
Enfermedades del Ano/epidemiología , Enfermedades del Ano/patología , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Infecciones por Papillomavirus/virología , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades del Ano/diagnóstico , Enfermedades del Ano/virología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Lesiones Precancerosas/diagnóstico , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at disproportionately high risk for anal cancer. There is no definitive approach to the management of high-grade squamous intraepithelial lesions (HSIL), which are precursors of anal cancer, and evidence suggests that posttreatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves HSIL treatment effectiveness. The objectives of this study were to evaluate the optimal HSIL management strategy with respect to clinical effectiveness and cost-effectiveness and to identify the optimal age for initiating HSIL management. METHODS: A decision analytic model of the natural history of anal carcinoma and HSIL management strategies was constructed for HIV-positive MSM who were 27 years old or older. The model was informed by the Surveillance, Epidemiology, and End Results-Medicare database and published studies. Outcomes included the lifetime cost, life expectancy, quality-adjusted life expectancy, cumulative risk of cancer and cancer-related deaths, and cost-effectiveness from a societal perspective. RESULTS: Active monitoring was the most effective approach in patients 29 years or younger; thereafter, HSIL treatment plus adjuvant qHPV vaccination became most effective. When cost-effectiveness was considered (ie, an incremental cost-effectiveness ratio [ICER] < $100,000/quality-adjusted life-year), do nothing was cost-effective until the age of 38 years, and HSIL treatment plus adjuvant qHPV vaccination was cost-effective beyond the age of 38 years (95% confidence interval, 34-43 years). The ICER decreased as the age at HSIL management increased. Outcomes were sensitive to the rate of HSIL regression or progression and the cost of high-resolution anoscopy and biopsy. CONCLUSIONS: The management of HSIL in HIV-positive MSM who are 38 years old or older with treatment plus adjuvant qHPV vaccination is likely to be cost-effective. The conservative approach of no treatment is likely to be cost-effective in younger patients. Cancer 2017;123:4709-4719. © 2017 American Cancer Society.
Asunto(s)
Neoplasias del Ano/prevención & control , Carcinoma in Situ/prevención & control , Análisis Costo-Beneficio , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Infecciones por Papillomavirus/prevención & control , Lesiones Precancerosas/prevención & control , Adulto , Neoplasias del Ano/economía , Neoplasias del Ano/virología , Carcinoma in Situ/economía , Carcinoma in Situ/virología , Estudios de Cohortes , Progresión de la Enfermedad , Estudios de Seguimiento , Infecciones por VIH/economía , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae , Infecciones por Papillomavirus/economía , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/administración & dosificación , Lesiones Precancerosas/economía , Lesiones Precancerosas/virología , Años de Vida Ajustados por Calidad de Vida , Resultado del Tratamiento , Vacunación/economía , Vacunación/estadística & datos numéricosRESUMEN
BACKGROUND: Anal canal high-grade squamous intraepithelial lesion (HSIL) is the precursor to anal cancer. Immunocompromised patients are at increased risk and disease is usually within 3 cm from the anal verge. High-resolution anoscopy (HRA) with an 8-cm anoscope is used to identify and guide cautery treatment of HSIL. PURPOSE: We report three patients with a long-term history of ulcerative colitis (UC) treated with systemic immunomodulators who developed proximally located rectal HSIL. RESULTS/OUTCOMES: Two patients were HIV-negative women, 63 and 48 years old, and the third was a 51-year-old HIV-positive man with underlying UC for 10, 16, and 3 years, respectively. They each presented with a HPV-positive HSIL visibly extending above the limits of the anoscope used for HRA. None developed cancer. All had episodes of active UC. It is unclear what causative role systemic immunomodulators play in predisposing UC patients to proximal HSIL. HSIL probably developed on a tongue of HPV-infected squamous epithelium growing proximally over the inflamed rectum. Islands developed when areas of squamous epithelium degenerated, creating skip areas. DISCUSSION: This study highlights the potential for HSIL to extend into the rectum either as a contiguous patch or isolated islands and the need for heightened surveillance in patients with extensive anal canal HSIL treated with immunodulator therapy. HSIL identified at the limit of the anoscope should be investigated further with colonoscopy, and argon plasma coagulation (APC) ablation can serve as an effective treatment option. Patients are at risk for stricture, but it is unclear what role the UC or the ablation played in stricture formation.
Asunto(s)
Carcinoma de Células Escamosas/patología , Colitis Ulcerosa/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Neoplasias del Recto/patología , Recto/patología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: Radiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia, but its efficacy in treating anal canal high-grade squamous intraepithelial lesions (HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy of applying hemi-circumferential RFA to anal canal HSIL. METHODS: Twenty-one HIV-negative participants with HSIL occupying ≤ half the anal canal circumference were treated with hemi-circumferential anal canal RFA. Participants were assessed every 3 months for 12 months with high-resolution anoscopy; recurrence in the treatment zone was re-treated with focal RFA. RESULTS: Twenty-one participants with a mean of 1.7 lesions (range 1-4) enrolled and completed the trial. Six (29 %) participants had recurrent HSIL within the treated hemi-circumference within 1 year. Four participants (19 %) had persistence of an index lesion at 3 months. One (2.9 %) index HSIL persisted again at 12 months. No participants had more than two RFA treatments. KM curve-predicted HSIL-free survival within the treatment zone at 1 year was 76 % (95 % CI 52-89 %). Comparing the first 7 and last 14 participants, the predicted 1-year HSIL-free survivals are 43 % (95 % CI 10-73 %) and 93 % (95 % CI 59-99 %), respectively (p = 0.008), suggesting a learning curve with the treating physician. Multivariable analysis showed decreased recurrence in the last 14 participants (HR 0.02; 95 % CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95 % CI 1.01-2.01). No participants had device or procedure-related serious adverse events, anal stricture, or heavy bleeding. CONCLUSIONS: Hemi-circumferential RFA yielded a high rate of anal HSIL eradication in HIV-negative patients at 1 year with minimal adverse events. Lesion persistence was probably related to incomplete initial ablation.
Asunto(s)
Neoplasias del Ano/cirugía , Carcinoma in Situ/cirugía , Ablación por Catéter , Adulto , Anciano , Ablación por Catéter/efectos adversos , Demografía , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/patología , Dolor Postoperatorio/etiología , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Perianal high-grade dysplasia (Bowen disease) is traditionally treated with mapping and wide excision with possible grafting rather than local ablation. OBJECTIVE: The aim of this study is to examine the results of high-grade perianal dysplasia ablation. DATA SOURCES: Data for this study were derived from a retrospective chart review at a surgical practice screening and treating patients for high-grade dysplasia between July 1998 and June 2013. STUDY SELECTION: The patients included were men who have sex with men and are undergoing perianal dysplasia ablation. INTERVENTION: Ablation of perianal dysplasia with electrocautery, laser, or infrared coagulation was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the recurrence of perianal dysplasia postablation and factors affecting recurrence. RESULTS: Seventy HIV-positive and 11 HIV-negative patients enrolled; the median ages were 44.7 and 42.8 years. Median follow-up times for HIV-positive and HIV-negative patients were 4.62 and 3.53 years, and the median numbers of treatments were 4 and 1, p = 0.004. The median number of lesions treated was 1 for both groups. Only 1 HIV-negative patient had a recurrence 8 months after treatment. For HIV-positive patients, the Kaplan-Meier probability of recurrence at 1, 3, and 5 years was 38% (95% CI 26-50), 59% (95% CI 47-72), and 68% (95% CI 55-81) after the first ablation with no difference for subsequent treatments. HIV-positive patients had a relative risk of perianal high-grade squamous intraepithelial lesions of 3.72 (95% CI 2.10-6.60) compared with HIV-negative patients (p ≤ 0.0001). In multivariate analysis, only each increase in intra-anal high-grade squamous intraepithelial lesions significantly increased recurrence (HR 1.13, 95% CI 1.00-1.28, p = 0.002). Only 3 patients with perianal high-grade squamous intraepithelial lesions did not have canal dysplasia. Perianal cancer developed in 3 after being lost to follow-up. LIMITATIONS: This is a retrospective analysis of 1 experienced surgeon's results. No precise way exists to accurately determine the size of the disease. CONCLUSIONS: Perianal dysplasia can be successfully ablated, but recurrence remains high. Almost all patients have anal canal dysplasia. HIV-positive patients are at the greatest risk for disease and recurrence. An increased number of high-grade canal lesions increases recurrence.
Asunto(s)
Neoplasias del Ano/cirugía , Enfermedad de Bowen/cirugía , Neoplasias Cutáneas/cirugía , Adulto , Anciano , Neoplasias del Ano/patología , Bisexualidad , Enfermedad de Bowen/patología , Electrocoagulación , Seropositividad para VIH , Homosexualidad Masculina , Humanos , Terapia por Láser , Fotocoagulación , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: The incidence of anal cancer is higher in women than men in the general population and has been increasing for several decades. Similar to cervical cancer, most anal cancers are associated with human papillomavirus (HPV), and it is believed that anal cancers are preceded by anal high-grade squamous intraepithelial lesions (HSIL). Our goals were to summarize the literature on anal cancer, HSIL, and HPV infection in women and to provide screening recommendations in women. METHODS: A group of experts convened by the American Society for Colposcopy and Cervical Pathology and the International Anal Neoplasia Society reviewed the literature on anal HPV infection, anal SIL, and anal cancer in women. RESULTS: Anal HPV infection is common in women but is relatively transient in most. The risk of anal HSIL and cancer varies considerably by risk group, with human immunodeficiency virus-infected women and those with a history of lower genital tract neoplasia at highest risk compared with the general population. CONCLUSIONS: While there are no data yet to demonstrate that identification and treatment of anal HSIL leads to reduced risk of anal cancer, women in groups at the highest risk should be queried for anal cancer symptoms and required to have digital anorectal examinations to detect anal cancers. Human immunodeficiency virus-infected women and women with lower genital tract neoplasia may be considered for screening with anal cytology with triage to treatment if HSIL is diagnosed. Healthy women with no known risk factors or anal cancer symptoms do not need to be routinely screened for anal cancer or anal HSIL.
Asunto(s)
Neoplasias del Ano/diagnóstico , Detección Precoz del Cáncer/métodos , Infecciones por Papillomavirus/diagnóstico , Lesiones Intraepiteliales Escamosas de Cuello Uterino/diagnóstico , Neoplasias del Ano/etiología , Neoplasias del Ano/terapia , Femenino , Humanos , Infecciones por Papillomavirus/complicaciones , Factores de Riesgo , Lesiones Intraepiteliales Escamosas de Cuello Uterino/complicaciones , Lesiones Intraepiteliales Escamosas de Cuello Uterino/terapiaRESUMEN
BACKGROUND: Colorectal surgeons are ideal referral sources to screen for and treat high-grade anal dysplasia (high-grade squamous intraepithelial lesion [HSIL]) and anal cancer. Anal cytology and high-resolution anoscopy (HRA) using acetic acid and magnification are optimal methods for screening. We endeavored to determine US colorectal surgeons' attitudes and practices regarding HSIL screening. METHODS: An Internet-based survey with questions related to clinician demographics and attitudes and practices regarding anal dysplasia was sent to US members of the American Society of Colon and Rectal Surgeons. RESULTS: Of 1655 requests, 290 (18%) eligible participants responded. Most were white (83%), male (76%), board-certified colorectal surgeons (89%), and graduating medical school after 1990 (54%), almost all treated patients at risk for anal cancer and had read research on HSIL. Approximately one-third of respondents had performed anal cytology, and one-third had performed HRA. When evaluating patients for HSIL in surgery, only 31% use acetic acid with magnification. Of 99 participants who perform HRA, 46% were formally trained, 83% primarily do HRA primarily in the operating room, and 82% use acetic acid with magnification. Knowledge of HSIL risk factors was not associated with screening. Women, more recent graduates, and surgeons with higher percentages of HIV-infected patients were more likely to screen. Screening barriers included no training (52%), not a priority (23%), lack of evidence (21%), and cost (8%). CONCLUSIONS: American Society of Colon and Rectal Surgeons members responding to the survey by and large do not screen for anal dysplasia. Those that do are often not formally trained and use inadequate technique.