The role of polymerase chain reaction of high-risk human papilloma virus in the screening of high-grade squamous intraepithelial lesions in the anal mucosa of human immunodeficiency virus-positive males having sex with males.

OBJECTIVES: To evaluate the advantages of cytology and PCR of high-risk human papilloma virus (PCR HR-HPV) infection in biopsy-derived diagnosis of high-grade squamous intraepithelial lesions (HSIL = AIN2/AIN3) in HIV-positive men having sex with men (MSM). METHODS: This is a single-centered study conducted between May 2010 and May 2014 in patients (n = 201, mean age 37 years) recruited from our outpatient clinic. Samples of anal canal mucosa were taken into liquid medium for PCR HPV analysis and for cytology. Anoscopy was performed for histology evaluation. RESULTS: Anoscopy showed 33.8% were normal, 47.8% low-grade squamous intraepithelial lesions (LSIL), and 18.4% HSIL; 80.2% had HR-HPV. PCR of HR-HPV had greater sensitivity than did cytology (88.8% vs. 75.7%) in HSIL screening, with similar positive (PPV) and negative predictive value (NPV) of 20.3 vs. 22.9 and 89.7 vs. 88.1, respectively. Combining both tests increased the sensitivity and NPV of HSIL diagnosis to 100%. Correlation of cytology vs. histology was, generally, very low and PCR of HR-HPV vs. histology was non-existent (<0.2) or low (<0.4). Area under the receiver operating characteristics (AUROC) curve analysis of cytology and PCR HR-HPV for the diagnosis of HSIL was poor (<0.6). Multivariate regression analysis showed protective factors against HSIL were: viral suppression (OR: 0.312; 95%CI: 0.099-0.984), and/or syphilis infection (OR: 0.193; 95%CI: 0.045-0.827). HSIL risk was associated with HPV-68 genotype (OR: 20.1; 95%CI: 2.04-197.82). CONCLUSIONS: When cytology and PCR HR-HPV findings are normal, the diagnosis of pre-malignant HSIL can be reliably ruled-out in HIV suppression with treatment protects against the appearance of HSIL [corrected].

Antiretroviral therapy as a factor protective against anal dysplasia in HIV-infected males who have sex with males.

OBJECTIVES: Chronic infection with oncogenic HPV genotype is associated with the development of anal dysplasia. Antiretroviral therapy (ART) has been shown to decrease the incidence of cervical carcinoma in women with HIV. We sought to: 1) describe the prevalence and grade of anal dysplasia and HPV infection in our study subjects; 2) analyze the grade of correlation between anal cytology, PCR of high-risk HPV, and histology; 3) identify the factors associated with the appearance of ≥ AIN2 lesions. DESIGN: Cross-sectional, prospective study. METHODS: A cohort of HIV-positive males (n = 140, mean age  = 37 years) who have sex with males (MSM) had epidemiological, clinical and analytical data collected. Anal mucosa samples were taken for cytology, HPV PCR genotyping, and anoscopy for histological analysis. RESULTS: Within the cohort, 77.1% were being treated with ART, 8.5% anoscopy findings were AIN2, and 11.4% carcinoma in situ; 74.2% had high-risk (HR), 59.7% low-risk (LR) HPV genotypes and 46.8% had both. The combination of cytology with PCR identifying HR-HPV better predicts the histology findings than either of these factors alone. Logistic regression highlighted ART as a protective factor against ≥ AIN2 lesions (OR: 0.214; 95%CI: 0.054-0.84). Anal/genital condylomas (OR: 4.26; 95%CI: 1.27-14.3), and HPV68 genotype (OR: 10.6; 95%CI: 1.23-91.47) were identified as risk factors. CONCLUSIONS: In our cohort, ART has a protective effect against dysplastic anal lesions. Anal/genital warts and HPV68 genotype are predictors of ≥ AIN2 lesions. Introducing PCR HPV genotype evaluation improves screening success over that of cytology alone.

Linfocitos CD4 como factor protector frente a la infección por genotipos oncogénicos del virus del papiloma humano en la mucosa del canal anal de varones que tienen sexo con varones infectados por el virus de la inmunodeficiencia humana / CD4 lymphocytes as a protective factor against infection by oncogenic genotypes of human papilloma virus in the anal mucosa of men who have sex with human immunodeficiency virus positive men

Fundamento y objetivos: Analizar la prevalencia de los genotipos del virus del papiloma humano (VPH) y de displasia de canal anal en una cohorte prospectiva de pacientes infectados por el virus de la inmunodeficiencia humana (VIH) que mantienen relaciones sexuales con varones (HSH) del sur de España, así como las variables que se asocian con la aparición de lesiones displásicas y genotipos de VPH oncogénicos. Pacientes y método: Estudio transversal compuesto por pacientes HSH-VIH positivos procedentes de una cohorte prospectiva de seropositivos atendidos en una Unidad de Enfermedades Infecciosas, incluidos de forma consecutiva tras firma de consentimiento informado. En la visita se recogían datos epidemiológicos, clínicos, analíticos, y se tomaban 2 muestras de la mucosa del canal anal: una para realización de polymerase chain reaction (PCR, «reacción en cadena de la polimerasa») de VPH, y otra para citología. La clasificación citológica empleada fue la de Bethesda. Resultados: Un total de 134 pacientes fueron incluidos de forma consecutiva, con edad media (DE) de 35,97 (9,5) años. El 16,4% (22/134) de las muestras procedentes de la mucosa anal para estudio de PCR de VPH no fueron válidas por falta de ADN en el material. Un total de 102/112 (91,1%) pacientes estaban colonizados por VPH; 73/112 (65,1%) por genotipos de bajo grado (VPH-BR), 74/112 (66,1%) por genotipos de alto grado (VPH-AR) y 51/112 (41,5%) de alto y bajo grado de malignidad. Los genotipos más prevalentes fueron el 6 (16/112), 11 (15/112), 16 (27/112), 18 (16/112), 51 (16/112) y 53 (17/112). De las 134 muestras enviadas para citología, en 8/134 (5,9%) hubo falta de muestra y en 91/126 (72,2%) eran displásicas, de las que 65/91 (71,4%) correspondían a lesiones intraepiteliales escamosas de bajo grado, 26/91 (23,1%) a células escamosas atípicas, y ninguna lesión intraepitelial escamosa de alto grado. En el análisis multivariante que analizaba los factores de riesgo asociados con la aparición de displasia en la mucosa anal encontramos asociación estadística con el tabaco (odds ratio [OR] 3,336; intervalo de confianza del 95% [IC 95%] 1,196-9,303; p = 0,02) y número de genotipos de VPH-AR (OR 2,229; IC 95% 1,387-3,811; p = 0,001). En cuanto a la presencia de genotipos oncogénicos de VPH, en el análisis multivariante encontramos que cifras de CD4 más bajas (OR 2,48; IC 95% 1,098-5,58; p = 0,029) se asociaban con la infección por tales virus. Conclusiones: La prevalencia de displasia en el canal anal de pacientes VIH-HSH de nuestra área es muy alta, presentándose fundamentalmente en fumadores y con mayor número de genotipos de VPH oncogénicos. La presencia de VPH-AR se asociaba con menores cifras de linfocitos CD4 (AU)

Background and objectives: To analyze the prevalence of human papillomavirus (HPV) genotypes and anal dysplasia in a cohort of human immunodeficiency virus (HIV) infected men who have sex with men (MSM) from southern Spain, and the variables associated with the appearance of dysplastic lesions and oncogenic HPV genotypes. Patients and methods: A cross-sectional study involving a prospective cohort of HIV-positive MSM included consecutively after signing an informed consent form. During the consultation 2 samples were taken from the anal mucosa: one for HPV detection using polymerase chain reaction (PCR), and the other for cytological evaluation; the Bethesda system was used to classify the cytology. Results: One hundred and thirty-four consecutive patients were included. 91.1% patients were colonized by HPV, 66.1% by high-grade types and 41.52% by genotypes of low and high-grade malignancy. The most prevalent genotypes were: 6, 11, 16, 18, 51 and 53. 72.2% samples sent for cytology showed dysplasia, of which 71.4% were low-grade squamous intraepithelial lesions, 23.1% were atypical squamous cell, and 0% was high-grade squamous intraepithelial lesions. The multivariate analysis of risk factors associated with the appearance of dysplasia revealed association with smoking (95% confidence interval [95% CI] 1.196-9.303; odds ratio [OR] 3.336; P = .02) and number of oncogenic HPV types (95% CI 1.387-3.811; OR 2.229; P = .001). With regard to the presence of oncogenic HPV genotypes the multivariate analysis showed a high CD4 cell count was a protective factor against infection by these viruses (95% CI 1.098-5.58; OR 2.48; P = .029).Conclusions: The prevalence of anal dysplasia among HIV-positive MSM in this study is very high, fundamentally in smokers and a high number of oncogenic HPV genotypes. The presence of oncogenic HPV genotypes was associated with a lower CD4 cell count (AU)

[CD4 lymphocytes as a protective factor against infection by oncogenic genotypes of human papillomavirus in the anal mucosa of men who have sex with human immunodeficiency virus positive men]. / Linfocitos CD4 como factor protector frente a la infección por genotipos oncogénicos del virus del papiloma humano en la mucosa del canal anal de varones que tienen sexo con varones infectados por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVES: To analyze the prevalence of human papillomavirus (HPV) genotypes and anal dysplasia in a cohort of human immunodeficiency virus (HIV) infected men who have sex with men (MSM) from southern Spain, and the variables associated with the appearance of dysplastic lesions and oncogenic HPV genotypes. PATIENTS AND METHODS: A cross-sectional study involving a prospective cohort of HIV-positive MSM included consecutively after signing an informed consent form. During the consultation 2 samples were taken from the anal mucosa: one for HPV detection using polymerase chain reaction (PCR), and the other for cytological evaluation; the Bethesda system was used to classify the cytology. RESULTS: One hundred and thirty-four consecutive patients were included. 91.1% patients were colonized by HPV, 66.1% by high-grade types and 41.52% by genotypes of low and high-grade malignancy. The most prevalent genotypes were: 6, 11, 16, 18, 51 and 53. 72.2% samples sent for cytology showed dysplasia, of which 71.4% were low-grade squamous intraepithelial lesions, 23.1% were atypical squamous cell, and 0% was high-grade squamous intraepithelial lesions. The multivariate analysis of risk factors associated with the appearance of dysplasia revealed association with smoking (95% confidence interval [95% CI] 1.196-9.303; odds ratio [OR] 3.336; P=.02) and number of oncogenic HPV types (95% CI 1.387-3.811; OR 2.229; P=.001). With regard to the presence of oncogenic HPV genotypes the multivariate analysis showed a high CD4 cell count was a protective factor against infection by these viruses (95% CI 1.098-5.58; OR 2.48; P=.029). CONCLUSIONS: The prevalence of anal dysplasia among HIV-positive MSM in this study is very high, fundamentally in smokers and a high number of oncogenic HPV genotypes. The presence of oncogenic HPV genotypes was associated with a lower CD4 cell count.