RESUMEN
Objective: Patients with pathogenic variants in the GATA Binding Protein 2 (GATA2), a hematopoietic transcription factor, are at risk for human papillomavirus-related (HPV) anogenital cancer at younger than expected ages. A female cohort with GATA2 haploinsufficiency was systematically assessed by two gynecologists to characterize the extent and severity of anogenital HPV disease, which was also compared with affected males. Methods: A 17-year retrospective review of medical records, including laboratory, histopathology and cytopathology records was performed for patients diagnosed with GATA2 haploinsufficiency followed at the National Institutes of Health. Student's t-test and Mann-Whitney U test or Fisher's exact test were used to compare differences in continuous or categorical variables, respectively. Spearman's rho coefficient was employed for correlations. Results: Of 68 patients with GATA2 haploinsufficiency, HPV disease was the initial manifestation in 27 (40%). HPV occurred at median 18.9 (15.2-26.2) years in females, and 25.6 (23.4-26.9) years in males. Fifty-two (76%), 27 females and 25 males, developed HPV-related squamous intraepithelial lesions (SIL) including two males with oral cancer. Twenty-one patients developed anogenital high-grade SIL (HSIL) or carcinoma (16 females versus 5 males, (59% versus 20%, respectively, p=0.005) at median 27 (18.6-59.3) years for females and 33 (16.5-40.1) years for males. Females were more likely than males to require >2 surgeries to treat recurrent HSIL (p=0.0009). Of 30 patients undergoing hematopoietic stem cell transplant (HSCT) to manage disease arising from GATA2 haploinsufficiency, 12 (nine females, three males) had persistent HSIL/HPV disease. Of these nine females, eight underwent peri-transplant surgical treatment of HSIL. Five of seven who survived post-HSCT received HPV vaccination and had no or minimal evidence of HPV disease 2 years post-HSCT. HPV disease persisted in two receiving immunosuppression. HPV disease/low SIL (LSIL) resolved in all three males. Conclusion: Females with GATA2 haploinsufficiency exhibit a heightened risk of recurrent, multifocal anogenital HSIL requiring frequent surveillance and multiple treatments. GATA2 haploinsufficiency must be considered in a female with extensive, multifocal genital HSIL unresponsive to multiple surgeries. This population may benefit from early intervention like HSCT accompanied by continued, enhanced surveillance and treatment by gynecologic oncologists and gynecologists in those with anogenital HPV disease.
Asunto(s)
Deficiencia GATA2 , Factor de Transcripción GATA2 , Predisposición Genética a la Enfermedad , Infecciones por Papillomavirus , Humanos , Femenino , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/complicaciones , Adulto , Masculino , Estudios Retrospectivos , Deficiencia GATA2/genética , Adolescente , Factor de Transcripción GATA2/genética , Factor de Transcripción GATA2/deficiencia , Adulto Joven , Neoplasias de los Genitales Femeninos/genética , Neoplasias de los Genitales Femeninos/virología , Neoplasias del Ano/genética , Neoplasias del Ano/etiología , Neoplasias del Ano/virología , Haploinsuficiencia , Papillomaviridae/genética , Virus del Papiloma HumanoRESUMEN
BACKGROUND: Anal cancer is caused by human papillomavirus (HPV), particularly HPV-16, and is preceded by anal high-grade squamous intraepithelial lesions (HSILs). The incidence of anal cancer is highest among men who have sex with men (MSM) living with HIV (MSMLWH) and increases with age. However, most previous studies of anal HPV infection and anal HSIL were performed on men under 50 years old, and relatively little is known about HSIL among older MSMLWH or MSM not living with HIV (MSM-Not-LWH). SETTING: We enrolled MSM who were aged 50+ during 2018-2022 in San Francisco, CA. METHODS: One hundred twenty-nine MSMLWH and 109 MSM-not-LWH participated. All participants had anal HPV DNA testing (Atila Biosystems) and high-resolution anoscopy with a biopsy of visible lesions. RESULTS: Among MSMLWH, 47% had anal HSIL, 19% had HPV-16, and 51% had other oncogenic anal HPV types (excluding HPV-16). Among MSM-not-LWH, 37% had anal HSIL, 22% had HPV-16, and 34% had other oncogenic anal HPV types. Increasing age was not statistically associated with prevalent HSIL, HPV-16, or other oncogenic HPV infections in MSMLWH or MSM-not-LWH. HPV-16 (odds ratio: 45.1, 95% confidence interval: 15.8-129); other oncogenic HPV types (odds ratio: 5.95, 95% confidence interval: 2.74-12.9) were associated with increased odds of anal HSIL, adjusted for age, income, education, and HIV status. CONCLUSION: The prevalence of oncogenic anal HPV, anal HPV-16, and anal HSIL remains very high in older MSMLWH and MSM-not-LWH. With recent evidence showing that treating anal HSIL prevents anal cancer, MSM aged 50+ should be considered for anal cancer screening.
Asunto(s)
Neoplasias del Ano , Infecciones por VIH , Homosexualidad Masculina , Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Humanos , Masculino , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/complicaciones , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Prevalencia , Lesiones Intraepiteliales Escamosas/virología , Lesiones Intraepiteliales Escamosas/epidemiología , Lesiones Intraepiteliales Escamosas/patología , Neoplasias del Ano/epidemiología , Neoplasias del Ano/virología , Anciano , San Francisco/epidemiología , Canal Anal/virología , Canal Anal/patología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificaciónAsunto(s)
Neoplasias del Ano , Carcinoma de Células Escamosas , Disbiosis , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas/virología , Neoplasias del Ano/virología , Infecciones por Papillomavirus/complicaciones , Microbiota , Masculino , Papillomaviridae/aislamiento & purificación , Femenino , Persona de Mediana Edad , Virus del Papiloma HumanoRESUMEN
We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSILs) in men who have sex with men living with human immunodeficiency virus and who underwent 3 visits over 2 years, with cytology and high-resolution anoscopy, within the ANRS-EP57-APACHES study. The cumulative HSIL detection rate was 33% (134 of 410), of which 48% HSILs were detected at baseline. HSIL detection varied considerably by center (from 13% to 51%). The strongest HSIL determinants were baseline human papillomavirus 16 (adjusted odds ratio, 8.2; 95% confidence interval, 3.6-18.9) and p16/Ki67 (4.6 [2.3-9.1]). Repeated annual cytology and high-resolution anoscopy improved HSIL detection but did not fully compensate for between-center heterogeneity.
Asunto(s)
Neoplasias del Ano , Infecciones por VIH , Homosexualidad Masculina , Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Humanos , Masculino , Infecciones por VIH/complicaciones , Lesiones Intraepiteliales Escamosas/virología , Lesiones Intraepiteliales Escamosas/patología , Francia/epidemiología , Adulto , Neoplasias del Ano/virología , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/epidemiología , Neoplasias del Ano/patología , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Estudios de Seguimiento , Canal Anal/virología , Canal Anal/patología , Papillomavirus Humano 16/aislamiento & purificación , Minorías Sexuales y de GéneroRESUMEN
Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy linked to high-risk human papillomavirus (HPV) infection, which develops from precursor lesions like low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions (HGSILs). ASCC incidence varies across populations and poses increased risk for people living with HIV. Our investigation focused on transcriptomic and metatranscriptomic changes from squamous intraepithelial lesions to ASCC. Metatranscriptomic analysis highlighted specific bacterial species (e.g., Fusobacterium nucleatum, Bacteroides fragilis) more prevalent in ASCC than precancerous lesions. These species correlated with gene-encoding enzymes (Acca, glyQ, eno, pgk, por) and oncoproteins (FadA, dnaK), presenting potential diagnostic or treatment markers. Unsupervised transcriptomic analysis identified distinct sample clusters reflecting histological diagnosis, immune infiltrate, HIV/HPV status, and pathway activities, recapitulating anal cancer progression's natural history. Our study unveiled molecular mechanisms in anal cancer progression, aiding in stratifying HGSIL cases based on low or high risk of progression to malignancy.
Asunto(s)
Neoplasias del Ano , Carcinoma de Células Escamosas , Transcriptoma , Humanos , Neoplasias del Ano/genética , Neoplasias del Ano/inmunología , Neoplasias del Ano/patología , Neoplasias del Ano/virología , Neoplasias del Ano/microbiología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/microbiología , Carcinoma de Células Escamosas/patología , Microbiota/inmunología , Masculino , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/inmunología , Lesiones Intraepiteliales Escamosas/genética , Lesiones Intraepiteliales Escamosas/patología , Lesiones Intraepiteliales Escamosas/virología , Femenino , Progresión de la Enfermedad , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunologíaRESUMEN
HPV16 is responsible for approximately 60% and 90% of global HPV-induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A-D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named "non-European" variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named "European variants") has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV-related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV-driven anogenital and head and neck cancers.
Asunto(s)
Neoplasias de Cabeza y Cuello , Papillomavirus Humano 16 , Infecciones por Papillomavirus , Filogenia , Humanos , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Neoplasias de Cabeza y Cuello/virología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/epidemiología , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/clasificación , Femenino , Variación Genética , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , Genoma Viral , Neoplasias del Ano/virología , Neoplasias del Ano/epidemiología , Masculino , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/genéticaRESUMEN
Lesbian, gay, bisexual, transgender, queer, or questioning individuals, as well as those with another diverse identity (LGBTQ+), present specific nuances in healthcare that physicians must consider in clinical practice. Particularly, gastroenterologists are nowadays facing different issues in several fields regarding LGBTQ+ healthcare, such as endoscopy, inflammatory bowel disease, hepatology, and proctology. In this study, the authors provide a practice-oriented and up-to-date review reinforcing the importance of some of the most prevalent pathologies associated with sexuality that gastroenterologists may encounter in their clinical practice. In terms of endoscopy, authors describe the endoscopic findings related to human papillomavirus (HPV) infection: the esophageal squamous papilloma and cell carcinoma; also highlight the importance of retroflexion maneuver during a routine colonoscopy that allows detection of anal intraepithelial neoplasia lesions that can be anal cancer precursors. Regarding inflammatory bowel disease, some considerations are made about the differential diagnosis with infectious proctitis, and the topic of the risk of anal cancer due to HPV infection, in this specific population, is also addressed. Considering hepatology, the authors review the most important issues related to hepatotropic sexually transmitted infections. The authors also make some comments regarding the possibility of drug-induced liver injury in gender-affirming hormone therapy and pre-exposure prophylaxis for HIV prevention. Finally, considering the proctology field, an up-to-date review is performed regarding anal cancer screening, HPV infection and related diseases, and infectious proctitis management.
Asunto(s)
Gastroenterología , Minorías Sexuales y de Género , Humanos , Femenino , Masculino , Enfermedades Inflamatorias del Intestino/terapia , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/virología , Neoplasias del Ano/terapia , Factores de Riesgo , Enfermedades de Transmisión Sexual/diagnósticoRESUMEN
This study aimed to provide comprehensive clinical screening data for anal intraepithelial neoplasia (AIN). This study included 312 patients who underwent high-resolution anoscopy (HRA) examinations between January 1, 2020 and April 15, 2024. Clinical data, including demographic information, clinical history, cytology/high-risk human papilloma virus (hrHPV) results, and HRA records, were analyzed. The median age of all patients was 42 years (interquartile range: 33-52 years). Approximately 26.3% reported a history of VIN2/3+, 13.5% had a history of VaIN2/3+, 29.8% had a history of CIN2/3+, 44.6% had persistent cervical HPV16 infection, and 12.5% had immune suppression. Among the 312 patients, 14.4% were diagnosed with AIN2/3, 25.0% with AIN1 and 60.6% were normal. Anal cytological abnormalities were found in 41.3% of all patients, with a significantly higher rate in AIN2/3 patients than in ≤AIN1, 71.1% versus 36.3%, p < 0.001. The hrHPV positivity rate was 89.7%, with HPV16 being the most prevalent. The complete agreement rate for HRA impressions was 79.5%. Multi-variable analysis revealed immune suppression (odds ratio [OR]: 3.47, 95% confidence interval [CI]: 1.42-8.5) and VIN2/3+ (OR: 2.82, 95% CI: 1.27-6.28) were independent risk factors for AIN2/3. Abnormal cytology results (OR: 3.3, 95% CI: 1.52-7.17) and anal HPV16 infection (OR: 3.2, 95% CI: 1.26-8.12) demonstrated similar ORs for AIN2/3. Early screening for AIN2/3+ is crucial in Chinese women with lower genital tract precancerous and cancerous lesions, particularly in those with VIN2/3+ and immune suppression.
Asunto(s)
Neoplasias del Ano , Carcinoma in Situ , Detección Precoz del Cáncer , Infecciones por Papillomavirus , Humanos , Femenino , Persona de Mediana Edad , Adulto , China/epidemiología , Neoplasias del Ano/virología , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/epidemiología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Detección Precoz del Cáncer/métodos , Carcinoma in Situ/epidemiología , Carcinoma in Situ/virología , Carcinoma in Situ/diagnóstico , Factores de Riesgo , Papillomavirus Humano 16/aislamiento & purificaciónRESUMEN
BACKGROUND: Solid organ transplant recipients are at an increased risk for anogenital Human Papillomavirus (HPV)-related disease, including anal high-grade squamous intraepithelial lesions (HSIL) and anal squamous cell cancer (ASCC). Guidelines for ASCC screening in transplant recipients are limited. Our aim was to understand current practice of ASCC screening in adult liver transplant (LT) candidates and recipients at transplant centers across the United States. METHODS: We surveyed medical directors of 113 LT centers across the United States which had publicly available contact information. The survey evaluated center perceptions on cancer and HPV disease risk in transplant populations, ASCC screening, barriers and facilitators for ASCC screening and HPV vaccination practices. RESULTS: We received 26/113 (23%) responses, of which 24 were complete and included in the analysis. Eleven of 24 (46%) centers reported screening for ASCC and 3/24 (12.5%) centers reported having formal guidelines. Centers who perform ASCC screening were more likely to perform transplants in people living with HIV and were more aware of the burden of HPV disease in transplant populations. All respondents believed that additional data on the impact of screening on ASCC incidence would support screening decisions. Increased access to specialists for screening/high-resolution anoscopy was also perceived as a facilitator. Only 7/24 (29%) centers regularly evaluated HPV vaccination status of their patients. CONCLUSION: This national survey of LT centers reveals non-standardized ASCC screening practices, and identified data, educational and resource needs to improve prevention of ASCC in this population.
Asunto(s)
Neoplasias del Ano , Detección Precoz del Cáncer , Trasplante de Hígado , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Humanos , Neoplasias del Ano/virología , Neoplasias del Ano/prevención & control , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/prevención & control , Estados Unidos/epidemiología , Trasplante de Hígado/efectos adversos , Detección Precoz del Cáncer/métodos , Encuestas y Cuestionarios , Vacunas contra Papillomavirus/administración & dosificación , Vacunas contra Papillomavirus/uso terapéutico , Femenino , Masculino , Tamizaje Masivo/métodos , Carcinoma de Células Escamosas/virología , Lesiones Intraepiteliales Escamosas/virología , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
BACKGROUND: People with HIV at highest risk of anal cancer include gay, bisexual, and other men who have sex with men and transgender women aged 35 years or older as well as other people with HIV aged 45 years or older. Identifying and treating precancerous lesions can reduce anal cancer incidence in these groups. We assessed the prevalence of anal cytology and access to high-resolution anoscopy among people with HIV overall and in those individuals at highest risk. METHODS: Data were obtained from the Centers for Disease Control and Prevention's Medical Monitoring Project, a population-based survey of people with HIV aged 18 years and older, and a supplemental Medical Monitoring Project facility survey. We report weighted percentages of people with HIV receiving anal cytology during the past 12 months, access to high-resolution anoscopy, and characteristics of HIV care facilities by availability of high-resolution anoscopy. RESULTS: Overall, 4.8% (95% confidence interval [CI]â= 3.4% to 6.1%) of people with HIV had undergone anal cytology in the prior 12 months. Only 7.7% (95% CIâ= 5.1% to 10.6%) of gay, bisexual, and other men who have sex with men as well as transgender women 35 years of age or older and 1.9% (95% CIâ=â0.9% to 2.9%) of all other people with HIV aged 45 years and older had anal cytology. Prevalence was statistically significantly low among people with HIV with the following characteristics: non-Hispanic or Latino, Black or African American, high school education or less, heterosexual orientation, and living in southern Medical Monitoring Project states. Among people with HIV, 32.8% (95% CIâ= 28.0% to 37.7%) had no access to high-resolution anoscopy on-site or through referral at their care facility; 22.2% (95% CIâ= 19.5% to 24.9%) had on-site access; 45.0% (95% CIâ= 41.5% to 48.5%) had high-resolution anoscopy available through referral. Most facilities that received Ryan White HIV/AIDS Program funding, cared for more than 1000 people with HIV, or provided on-site colposcopy also provided high-resolution anoscopy on-site or through referral. CONCLUSIONS: Rates of anal cytology and access to high-resolution anoscopy were low among people with HIV, including those individuals at highest risk of anal cancer. Our data may inform large-scale implementation of anal cancer prevention efforts.
Asunto(s)
Neoplasias del Ano , Infecciones por VIH , Humanos , Masculino , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Neoplasias del Ano/epidemiología , Neoplasias del Ano/patología , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/virología , Persona de Mediana Edad , Adulto , Prevalencia , Estados Unidos/epidemiología , Detección Precoz del Cáncer/métodos , Canal Anal/patología , Canal Anal/virología , Accesibilidad a los Servicios de Salud , Adulto Joven , Anciano , Adolescente , Citodiagnóstico/métodos , Personas Transgénero/estadística & datos numéricos , Proctoscopía , Minorías Sexuales y de Género/estadística & datos numéricos , Tamizaje Masivo/métodos , CitologíaRESUMEN
BACKGROUND: Anal cancer risk is elevated among people with HIV. Recent anal cancer incidence patterns among people with HIV in the United States and Canada remain unclear. It is unknown how the incidence patterns may evolve. METHODS: Using data from the North American AIDS Cohort Collaboration on Research and Design, we investigated absolute anal cancer incidence and incidence trends nationally in the United States and Canada and in different US regions. We further estimated relative risk compared with people without HIV, relative risk among various subgroups, and projected future anal cancer burden among American people with HIV. RESULTS: Between 2001 and 2016 in the United States, age-standardized anal cancer incidence declined 2.2% per year (95% confidence interval = â4.4% to â0.1%), particularly in the Western region (â3.8% per year, 95% confidence interval = â6.5% to â0.9%). In Canada, incidence remained stable. Considerable geographic variation in risk was observed by US regions (eg, more than 4-fold risk in the Midwest and Southeast compared with the Northeast among men who have sex with men who have HIV). Anal cancer risk increased with a decrease in nadir CD4 cell count and was elevated among those individuals with opportunistic illnesses. Anal cancer burden among American people with HIV is expected to decrease through 2035, but more than 70% of cases will continue to occur in men who have sex with men who have HIV and in people with AIDS. CONCLUSION: Geographic variation in anal cancer risk and trends may reflect underlying differences in screening practices and HIV epidemic. Men who have sex with men who have HIV and people with prior AIDS diagnoses will continue to bear the highest anal cancer burden, highlighting the importance of precision prevention.
Asunto(s)
Neoplasias del Ano , Infecciones por VIH , Humanos , Neoplasias del Ano/epidemiología , Neoplasias del Ano/virología , Masculino , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Incidencia , Femenino , Persona de Mediana Edad , Adulto , Canadá/epidemiología , Estados Unidos/epidemiología , Factores de Riesgo , Homosexualidad Masculina/estadística & datos numéricos , América del Norte/epidemiología , AncianoRESUMEN
The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide.
Asunto(s)
Papillomaviridae , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Vacunas contra Papillomavirus/administración & dosificación , Femenino , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Papillomaviridae/patogenicidad , Neoplasias/virología , Vacunación , Neoplasias del Ano/prevención & control , Neoplasias del Ano/virología , Neoplasias del Ano/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Infecciones por VIH/prevención & control , Neoplasias Orofaríngeas/virología , Neoplasias Orofaríngeas/prevención & control , Masculino , Virus del Papiloma HumanoRESUMEN
Persistent infection with high-risk human papillomavirus (HPV) is recognized as the main cause for the development of anogenital cancers. This study prospectively evaluated the diagnostic performance of the novel Allplex-HPV28 assay with the Anyplex-II-HPV28 to detect and genotype HPV in 234 consecutive swabs and 32 biopsies of the anogenital tract from 265 patients with atypical findings in cytomorphological screening. Agreement in HPV-DNA detection between the Anyplex-II and Allplex-HPV28 assays was 99%. There was a notable diversity in the HPV-virome, with the most prevalent high-risk HPV types being 16, 53, 66, and 68. The agreement rates for detecting these genotypes exceeded 93% between the Anyplex-II and Allplex-HPV28 assays. Discrepancies in test results were solely noted for Anyplex-II-HPV28 results with a low signal intensity of "+", and for Allplex-HPV28 results with cycle thresholds of ≥36. The semi-quantitative analysis of HPV-DNA loads showed significant agreement between the Anyplex-II-HPV28 and Allplex-HPV28 assays (p < 0.001). Furthermore, HPV-DNA detection rates and mean HPV-DNA loads significantly correlated with the grade of abnormal changes identified in cytopathological assessment, being highest in cases of HSIL, condyloma accuminatum, and squamous cell carcinoma. Overall agreement rates for detecting specific HPV-types among the Anyplex-II and Allplex-HPV28 assays exceeded 99.5% in cases of atypical squamous cells, condyloma accuminatum, and squamous cell carcinoma. The novel Allplex-HPV28 assay shows good diagnostic performance in detecting and genotyping HPV commonly associated with anogenital cancers. Consequently, this assay could offer substantial potential for incorporation into future molecular screening programs for anogenital cancers in clinical settings.
Asunto(s)
Detección Precoz del Cáncer , Genotipo , Papillomaviridae , Infecciones por Papillomavirus , Humanos , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Femenino , Masculino , Papillomaviridae/genética , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Adulto , Anciano , Estudios Prospectivos , Técnicas de Diagnóstico Molecular/métodos , ADN Viral/genética , Técnicas de Genotipaje/métodos , Adulto Joven , Sensibilidad y Especificidad , Neoplasias del Ano/virología , Neoplasias del Ano/diagnóstico , Virus del Papiloma Humano , AlphapapillomavirusRESUMEN
Immunodeficiency predisposes to severe manifestations of human papillomavirus (HPV) infection, including extensive, recalcitrant anogenital lesions and their progression towards carcinomas. This holds for primary and acquired immunodeficiencies, and post-transplant immunosuppressive therapy. About 50% to 90% of patients receiving chronic immunosuppression after allogenic transplantation develop HPV-associated lesions within 4 to 5 years, comprising 10% to 15% of patients presenting with (pre)cancerous HPV-dependent anogenital lesions. Immunodeficiency is one of the highest risk factors associated with severe clinical manifestations of HPV-associated cancers. The primary objective of this work is to compare the long-term therapeutic effectiveness of surgical intervention for HPV-dependent lesions in transplant recipients undergoing chronic immunosuppression and patients burdened with primary or acquired immunodeficiencies. Two groups of 30 patients (selected for most extensive presentations of HPV-dependent neoplastic anogenital lesions), who underwent surgical treatment of these lesions were followed up for 3 to 5 years. The first group comprised patients who qualified and underwent kidney or liver transplantation (10 for a rare disease indication) and are under chronic immunosuppressive regimens. The second group comprised patients burdened by primary or acquired immunodeficiency (15 each). The recurrence rate in the follow-up period was the primary compared parameter. The recurrence rate was higher in the second group, amounting to >15%. For the first group a <5% recurrence rate was observed for recipients without rare disease indications, compared to <15% for recipients with such indications. The importance of rapid surgical intervention and the need for postoperative monitoring for recurrence is highlighted. Chronic immunosuppression demonstrates high relative safety and efficacy in terms of HPV-dependent anogenital lesion recurrence.
Asunto(s)
Infecciones por Papillomavirus , Humanos , Masculino , Infecciones por Papillomavirus/cirugía , Infecciones por Papillomavirus/complicaciones , Persona de Mediana Edad , Femenino , Resultado del Tratamiento , Adulto , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Neoplasias del Ano/cirugía , Neoplasias del Ano/virología , Trasplante de Hígado , Trasplante Homólogo , Factores de Tiempo , Virus del Papiloma HumanoRESUMEN
Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV.
Asunto(s)
Anticuerpos Antivirales , Infecciones por VIH , Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Humanos , Masculino , Femenino , Sudáfrica/epidemiología , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/inmunología , Persona de Mediana Edad , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Proteínas Oncogénicas Virales/inmunología , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Papillomavirus Humano 16/inmunología , Anciano , Neoplasias Orofaríngeas/virología , Neoplasias Orofaríngeas/epidemiología , Estudios Seroepidemiológicos , Estudios de Casos y Controles , Papillomavirus Humano 18/inmunología , Neoplasias de la Vulva/virología , Neoplasias de la Vulva/epidemiología , Neoplasias de la Vulva/sangre , Neoplasias del Pene/virología , Neoplasias del Pene/epidemiología , Neoplasias del Pene/sangre , Neoplasias del Ano/virología , Neoplasias del Ano/epidemiología , Neoplasias del Ano/sangre , Neoplasias Vaginales/virología , Neoplasias Vaginales/epidemiología , Población Negra , Proteínas Represoras/inmunología , Neoplasias/epidemiología , Neoplasias/virología , Neoplasias/sangre , Neoplasias/inmunología , Virus del Papiloma HumanoRESUMEN
Anal intraepithelial neoplasia (AIN) are precancerous lesions and are sequela of human papilloma virus (HPV) infection. AIN is classified as low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion. Screening with anal cytology and anoscopy should be considered for high-risk populations. Diagnosis is made through high resolution anaoscopy and biopsy. Options for treatment include ablation and several topical therapies; however, recurrence rates are high for all treatment options, and an ongoing surveillance is necessary to prevent progression to anal squamous cell carcinoma. HPV vaccination is recommended to prevent disease.
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Neoplasias del Ano , Condiloma Acuminado , Infecciones por Papillomavirus , Humanos , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/terapia , Neoplasias del Ano/patología , Neoplasias del Ano/virología , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/terapia , Carcinoma in Situ/patología , Carcinoma in Situ/virología , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/terapia , Condiloma Acuminado/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Lesiones Precancerosas/terapia , Lesiones Precancerosas/virología , Lesiones Intraepiteliales Escamosas/diagnóstico , Lesiones Intraepiteliales Escamosas/patología , Lesiones Intraepiteliales Escamosas/virologíaRESUMEN
INTRODUCTION: Dual immunostaining for p16/Ki67 is FDA-approved for use on liquid-based cervical cytology specimens; however, the utility of dual staining in anal cytology especially for ASCUS risk stratification is not well established. METHODS: We investigated dual staining performance on anal cytology specimens and correlated with subsequent cytologic interpretation, high-risk HPV status, and anal biopsy results. Dual staining for p16/Ki-67 was performed on all liquid-based anal cytology specimens from December 2021 to June 2022 (n = 43). RESULTS: Three patients had high grade squamous intraepithelial lesion (HSIL/AIN2-3) on biopsy; dual staining was positive in all three cases. All HR-HPV negative cases were negative for dual staining. Among the 12 ASCUS samples with subsequent anal biopsy results all also had HR-HPV testing. Due to small sample size of cases with squamous intraepithelial lesion (SIL) diagnosed on biopsy, the sensitivity and positive predictive value was not calculated. However, the specificity and negative predictive value of p16/Ki-67 dual staining for SIL of any grade on biopsy were 1 (95% CI: 0.66-1) and 0.9 (95% CI: 0.65-0.97) respectively, whereas the specificity and negative predictive value of HR-HPV testing for SIL of any grade on biopsy were 0.44 (95% CI: 0.14-0.79) and 0.8 (95% CI: 0.41-0.96) respectively. CONCLUSION: Dual p16/Ki-67 staining indicates transforming HPV infection and could help serve as an ancillary test for risk stratification for atypical anal cytology specimens. Among ASCUS samples, dual staining was specific for SIL of any grade with a high negative predictive value and therefore could be useful in clinical practices with limited availability for follow-up care.
Asunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina , Antígeno Ki-67 , Humanos , Canal Anal/patología , Canal Anal/virología , Neoplasias del Ano/patología , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/virología , Biomarcadores de Tumor/aislamiento & purificación , Biomarcadores de Tumor/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/aislamiento & purificación , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Citodiagnóstico/métodos , Inmunohistoquímica/métodos , Antígeno Ki-67/aislamiento & purificación , Antígeno Ki-67/metabolismo , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Sensibilidad y Especificidad , Lesiones Intraepiteliales Escamosas/patología , Lesiones Intraepiteliales Escamosas/virología , Lesiones Intraepiteliales Escamosas/diagnósticoRESUMEN
Background Anal cancer disproportionately affects sexual and gender minority individuals living with HIV. High-resolution anoscopy (HRA) is an in-clinic procedure to detect precancerous anal lesions and cancer, yet prospective data on factors associated with HRA attendance are lacking. We examined whether anal HPV sampling at home versus in a clinic impacts HRA uptake and assessed HRA acceptability. Methods Sexual and gender minority individuals were randomised to home-based self-sampling or clinical sampling. All were asked to attend in-clinic HRA 1year later. We regressed HRA attendance on study arm using multivariable Poisson regression and assessed HRA acceptability using χ 2 tests. Results A total of 62.8% of 196 participants who engaged in screening attended HRA. Although not significant (P =0.13), a higher proportion of participants who engaged in clinic-based screening attended HRA (68.5%) compared to home-based participants (57.9%). Overall, HRA uptake was higher among participants with anal cytology history (aRR 1.40, 95% CI 1.07-1.82), and lower among participants preferring a versatile anal sex position versus insertive (aRR 0.70, 95% CI 0.53-0.91), but did not differ by race or HIV serostatus. In the clinic arm, persons living with HIV had lower HRA attendance (42.9%) versus HIV-negative participants (73.3%) (P =0.02) and Black non-Hispanic participants had lower HRA attendance (41.7%) than White non-Hispanic participants (73.1%), (P =0.04). No differences in attendance by race or HIV status were observed in the home arm. Conclusions HRA uptake differed significantly by race and HIV status in the clinic arm but not the home arm.
Asunto(s)
Neoplasias del Ano , Infecciones por Papillomavirus , Humanos , Masculino , Neoplasias del Ano/prevención & control , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/virología , Femenino , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/diagnóstico , Adulto , Persona de Mediana Edad , Manejo de Especímenes/métodos , Minorías Sexuales y de Género/estadística & datos numéricos , Canal Anal/virología , Aceptación de la Atención de Salud/estadística & datos numéricos , Proctoscopía , Detección Precoz del Cáncer , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Autocuidado , Virus del Papiloma HumanoRESUMEN
People living with HIV (PLWH) are at highest risk of anal cancer and will benefit from optimized screening for early disease detection. We compared host DNA methylation markers in high-grade squamous intraepithelial lesions (HSIL) versus samples negative for intraepithelial lesions (NILM) or low-grade intraepithelial lesions (LSIL) in PLWH. We recruited PLWH identifying as male aged ≥18 years undergoing high-resolution anoscopy (HRA) in Seattle, Washington, 2015-2016. Anal brush samples were collected for HPV detection, genotyping, and pyrosequencing methylation (host genes ASCL1, PAX1, FMN2, and ATP10A); clinical data were abstracted from medical records. We assessed associations between methylation and presence and extent of HSIL using generalized estimating equation logistic regression, adjusting for age, CD4 count and HIV viral load. Marker panels using HPV DNA and methylation were also evaluated to predict prevalent HSIL. We analyzed 125 samples from 85 participants (mean age 50.1; standard deviation 11.0 years). ASCL1 (adjusted odds ratio [aOR] per 1 unit increase mean percent methylation: 1.07, 95% CI: 1.01-1.13) and FMN2 (aOR per 1 unit increase mean percent methylation: 1.14, 95% CI: 1.08-1.20) methylation were significantly associated with HSIL versus NILM/LSIL. ASCL1 (aOR: 1.06, 95% CI: 1.01-1.11) and FMN2 (aOR: 1.13, 95% CI: 1.08-1.17) methylation were positively associated with increasing HSIL extent. A panel combining methylation (ASCL1 and FMN2) and HPV DNA (HPV16, HPV18, and HPV31) demonstrated best balance of sensitivity (78.2%) and specificity (73.9%) for HSIL detection compared with methylation or HPV alone. Increasing levels of DNA methylation of ASCL1 and FMN2 were positively associated with HSIL detection in PLWH. Host gene methylation testing shows promise for HSIL screening and triage.