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BACKGROUND: Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune system in cancer development. In this systematic review and meta-analysis, we expand previous analyses of cancer risk for these two immunocompromised populations. METHODS: We considered studies published in English and listed on PubMed or Embase up to July 1, 2022. Studies were eligible for inclusion if they used population-based registries and compared cancer incidence in PLHIV or solid organ transplant recipients with the general population in the same geographical area. We extracted the number of observed site-specific cancers and expected cases and calculated meta-standardised incidence ratios for cancer within PLHIV and solid organ transplant recipients. In solid organ transplant recipients meta-standardised incidence ratios were compared by organ type. This project is registered on PROSPERO, CRD42022366679. FINDINGS: 46 studies in PLHIV and 67 in solid organ transplant recipients were included in the analysis. Meta-standardised incidence ratios for cancers associated with human papillomavirus were increased in both populations; the highest meta-standardised incidence ratio in PLHIV was anal cancer (37·28 [95% CI 23·65-58·75], I2=97·4%), and in solid organ transplant recipients was cutaneous squamous cell carcinoma (45·87 [31·70-66·38], I2=99·0%). Meta-standardised incidence ratios were significantly increased for most non-HPV viral-infection-related cancers in both populations; the highest standard incidence ratios were for Kaposi sarcoma (PLHIV: 801·52 [95% CI 200·25-3208·13], I2=100·0%; solid organ transplant recipients: 47·31 [23·09-96·95], I2=87·7%) and non-Hodgkin lymphoma (32·53 [19·64-53·87], I2=99·8%; 10·24 [8·48-12·35], I2=94·9%). Eight types of cancer with no known viral cause showed an increased risk in solid organ transplant recipients only; no cancer type showed increased risk in PLHIV only. INTERPRETATION: Cancer risk was increased for a range of infection-related cancers in both PLHIV and solid organ transplant recipients, but divergent results in these and other cancers have emerged. The cancer risk patterns probably reflect variances in the degree of impaired immunity, exposure to carcinogenic viruses, and perhaps exposure to carcinogenic immunosuppressive agents. FUNDING: US National Cancer Institute, National Institutes of Health.
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Infecciones por VIH , Neoplasias , Trasplante de Órganos , Receptores de Trasplantes , Humanos , Trasplante de Órganos/efectos adversos , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Neoplasias/epidemiología , Incidencia , Receptores de Trasplantes/estadística & datos numéricos , Huésped Inmunocomprometido , Factores de Riesgo , Medición de Riesgo , Femenino , MasculinoRESUMEN
Anal squamous cell carcinoma (ASCC) incidence is increasing globally. International consensus guidelines published in 2024 include HPV and/or cytology testing of anal swabs in those at greatest risk of ASCC. Self-collected anal swabs may be important for increasing screening uptake, but evidence is needed as to their equivalence to clinician-collected swabs. We searched Medline, Embase, Cochrane Library, and CINAHL databases for publications to 13 June 2023. Studies were included if reporting data on HPV testing, cytology testing, or acceptability, for both self- and clinician-collected anal swabs. Risk of bias was assessed using the QUADAS-2 assessment tool. The primary outcome was HPV and cytology sampling adequacy. Secondary outcomes were HPV and cytology results, and acceptability of collection methods. Thirteen papers describing 10 studies were eligible. Sample adequacy was comparable between self- and clinician-collected swabs for HPV testing (meta-adequacy ratio: 1.01 [95% CI 0.97-1.05]) but slightly lower for cytology by self-collection (meta-adequacy ratio: 0.91 [95% CI 0.88-0.95]). There was no significant difference in prevalence (meta-prevalence ratio: 0.83 (95% CI 0.65-1.07) for any HR-HPV, 0.98 (95% CI 0.84-1.14) for any HPV, and 0.68 (95% CI 0.33-1.37) for HPV16), or any cytological abnormality (meta-prevalence ratio 1.01 [95% CI 0.86-1.18]). Only three papers reported acceptability results. Findings indicate self-collection gives equivalent sample adequacy for HPV testing and ~ 10% inferior adequacy for cytological testing. Meta-prevalence was similar for HPV and cytology, but confidence intervals were wide. Larger studies are required to definitively assess use of self-collected swabs in anal cancer screening programs, including acceptability.
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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.
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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
ABSTRACT: We investigated factors associated with "worse than usual" anal health among gay and bisexual men aged ≥35 years recruited to a longitudinal study of anal human papillomavirus infection/lesions from September 2010 to August 2015.Among 616 participants (median age 49 years; 36% HIV-positive), 42 (6.8%) reported worse than usual anal health in the last 4 weeks. Associated factors included spending less time with gay friends (odds ratio [OR] = 2.25, 95% CI = 1.06-4.77), most time "feeling down"(OR = 9.17, 95% CI = 2.94-28.59), reduced libido (OR = 2.90, 95% CI = 1.52-5.52), current anal symptoms (OR = 6.55, 95% CI = 2.54-16.90), recent anal wart diagnosis (OR = 4.33, 95% CI = 1.98-9.49), and fear of developing anal cancer (OR = 9.34, 95% CI = 4.52-19.28).Concerns regarding anal health should be routinely discussed by clinicians, and potentially associated psychosocial, physical, and sexual issues further explored.
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Homosexualidad Masculina , Humanos , Masculino , Estudios Transversales , Persona de Mediana Edad , Adulto , Estudios Longitudinales , Anciano , Homosexualidad Masculina/estadística & datos numéricos , Homosexualidad Masculina/psicología , Minorías Sexuales y de Género/estadística & datos numéricos , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/complicaciones , Neoplasias del Ano/epidemiologíaRESUMEN
BACKGROUND: Gay and bisexual men (GBM) are at increased risk of human papillomavirus (HPV)-associated anal high-grade squamous intraepithelial lesions (HSILs). Understanding the fractions of HSILs attributable to HPV genotypes is important to inform potential impacts of screening and vaccination strategies. However, multiple infections are common, making attribution of causative types difficult. Algorithms developed for predicting HSIL-causative genotype fractions have never been compared with a reference standard in GBM. METHOD: Samples were from the Study of the Prevention of Anal Cancer. Baseline HPV genotypes detected in anal swab samples (160 participants) were compared with HPV genotypes in anal HSILs (222 lesions) determined by laser capture microdissection (LCM). Five algorithms were compared: proportional, hierarchical, maximum, minimum, and maximum likelihood estimation. RESULTS: All algorithms predicted HPV-16 as the most common HSIL-causative genotype, and proportions differed from LCM detection (37.8%) by algorithm (with differences of -6.1%, +20.9%, -20.4%, +2.9%, and +2.2% respectively). Fractions predicted using the proportional method showed a strong positive correlation with LCM, overall (R = 0.73 and P = .002), and by human immunodeficiency virus (HIV) status (HIV positive, R = 0.74 and P = .001; HIV-negative, R = 0.68 and P = .005). CONCLUSIONS: Algorithms produced a range of inaccurate estimates of HSIL attribution, with the proportional algorithm performing best. The high occurrence of multiple HPV infections means that these algorithms may be of limited use in GBM.
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Neoplasias del Ano , Infecciones por VIH , Seropositividad para VIH , Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Masculino , Humanos , Virus del Papiloma Humano , Homosexualidad Masculina , Infecciones por Papillomavirus/epidemiología , Genotipo , Neoplasias del Ano/diagnóstico , Papillomaviridae/genética , Infecciones por VIH/complicacionesRESUMEN
BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.
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Enfermedades del Ano , Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Homosexualidad Masculina , Virus del Papiloma Humano , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Incidencia , Conducta Sexual , Canal Anal , Enfermedades del Ano/diagnóstico , Estudios Longitudinales , Neoplasias del Ano/complicaciones , Papillomavirus Humano 16/genética , VIH , Papillomaviridae/genéticaRESUMEN
OBJECTIVES: Anal squamous cell carcinoma (ASCC) has a higher incidence described in certain groups, namely, in women with vulvar high-grade squamous intraepithelial lesions (vHSILs) and/or human papillomavirus squamous cell carcinoma (VSCC). This review describes terminology, vHSIL, and VSCC in their association with ASCC and the published recommendations for early detection of this cancer in these women. MATERIALS AND METHODS: A narrative review was conducted by the authors on vHSIL and VSCC as risk factors for ASCC. RESULTS: The ASCC and VSCC incidence are increasing. Women with vHSIL and/or VSCC can present with ASCC at diagnosis, being one of the highest-risk groups. Suspicious symptoms include rectal bleeding, pain, and a sensation of an anal mass. Digital anorectal examination can help detect early ASCC. Sensitivity of anal cytology in women with vHSIL and VSCC seems low, with the exception of immunosuppressed women with genital neoplasia (cervix, vagina, and vulva). There are still insufficient data on high-resolution anoscopy in women with vHSIL and/or VSCC as a screening method. CONCLUSIONS: Clinicians need be aware that women with vHSIL and VSCC comprise one of the highest-risk groups for ASCC. Inquiring suggestive symptoms of ASCC and a digital anorectal examination can help in the early detection of this type of cancer.
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Neoplasias del Ano , Carcinoma in Situ , Lesiones Intraepiteliales Escamosas , Neoplasias de la Vulva , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/epidemiología , Femenino , Humanos , Factores de Riesgo , Neoplasias de la Vulva/diagnóstico , Neoplasias de la Vulva/epidemiologíaRESUMEN
BACKGROUND: Incidence of anal cancer is highest in gay and bisexual men (GBM). Better understanding of the natural history of anal high-risk human papillomavirus (hrHPV) infection is needed for anal cancer prevention. METHODS: The Study of the Prevention of Anal Cancer was a 3-year study of Australian GBM, aged 35 years or older. We examined incidence, clearance, and risk factors for 13 hrHPV types at baseline and 3 annual visits. RESULTS: In 525 men with ≥ 2 visits, 348 (66.3%) acquired ≥ 1 incident hrHPV infection. HPV16 incidence rates were similar, but non-16 hrHPV incidence was higher in HIV-positive (51.8/100 person years [PY]) than HIV-negative men (36.5/100 PY, Pâ <â .001). Annual clearance rates of HPV16 (13.21/100 PY, 95% confidence interval, 10.53-16.56) were lower than for other hrHPV types. hrHPV clearance rates were not associated with HIV overall but were significantly lower in those with a lower nadir CD4 (<200 cells/µL) for HPV16 (Pâ =â .015) and other hrHPV types (Pâ =â .007). CONCLUSIONS: Higher incidence of non-16 hrHPV types, coupled with lower clearance of non-16 hrHPV types in those with past impaired immune function, is consistent with the greater role of non-16 hrHPV in anal cancer in HIV-positive people. AUSTRALIA NEW ZEALAND CLINICAL TRIALS REGISTRY: ANZCTR365383.
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Enfermedades del Ano , Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Adulto , Canal Anal , Enfermedades del Ano/epidemiología , Neoplasias del Ano/epidemiología , Australia/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Papillomavirus Humano 16 , Humanos , Masculino , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL). METHODS: The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs. RESULTS: Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5-13.5 per 100 PY). Significant bivariate predictors of higher incidence included age <45 years (HR 1.64, 95% CI 1.11-2.41), HIV positivity (HR 1.43, 95% CI .99-2.06), prior SIL diagnosis (P-trend < .001) and human papillomavirus (HPV)16 (HR 3.39, 2.38-4.84). Over 695.3 PY follow-up, 153 HSIL cleared (clearance 22.0, 95% CI 18.8-25.8 per 100 PY). Predictors were age < 45 years (HR 1.52, 1.08-2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29-2.49), smaller lesions (HR 1.62, 1.11-2.36) and no persistent HPV16 (HR 1.72, 1.23-2.41). There was 1 progression to cancer (incidence 0.224, 95% CI .006-1.25 per 100 PY). CONCLUSION: These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments. CLINICAL TRIALS REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR365383).
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Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Lesiones Intraepiteliales Escamosas , Anciano , Canal Anal , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/epidemiología , Bisexualidad , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiologíaRESUMEN
Background Anal symptoms may indicate serious pathology. Receptive anal intercourse (RAI) and sexually transmissible infections (STIs) may contribute to a higher prevalence of symptoms among gay and bisexual men (GBM). This study investigated associations with anal symptoms among GBM. METHODS: The Study of the Prevention of Anal Cancer was a longitudinal study of anal human papillomavirus and related lesions in Sydney, Australia. GBM aged ≥35 years were recruited from community settings between September 2010 and August 2015. Information about anal symptoms (discharge, itch, pain defecating, lump, bleeding, 'sores', tearing, tenesmus), STIs and sexual behaviours was collected. High-resolution anoscopy (HRA) and STI testing were performed. Logistic regression analyses on baseline data were performed to assess associations with each symptom. RESULTS: Among 616 participants (median age 49 years, 35.9% HIV positive), 35.3% reported at least one anal symptom within the past week and 65.3% were diagnosed with fistula, fissure, ulcer, warts, haemorrhoids and/or perianal dermatoses at HRA. Anal symptoms were not associated with anal chlamydia, gonorrhoea, warts or syphilis. Self-reported 'sores' were associated with previous anal herpes simplex virus (HSV; P < 0.001). 'Sores' (P < 0.001), itch (P = 0.019), discharge (P = 0.032) and lump (P = 0.028) were independently associated with ulceration. Among participants diagnosed with fissure, fistulae, haemorrhoids and perianal dermatoses, 61.9%, 100%, 62.0% and 63.9% respectively were asymptomatic. Only self-reported anal tear was independently associated with recent RAI. CONCLUSIONS: Previous anal HSV was the only STI associated with any symptom. Anal pathology was highly prevalent, but often asymptomatic. Anal symptoms do not appear to be useful markers of most anal pathology in GBM.
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Homosexualidad Masculina , Minorías Sexuales y de Género , Adulto , Estudios Transversales , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , AutoinformeRESUMEN
Recreational drug use (RDU) among gay and bisexual men (GBM) is associated with higher-risk sexual behaviours, however this has not been well defined among older GBM. We investigated the association between RDU and sexual behaviours among older GBM in Sydney, Australia. 617 GBM aged 35-79 years self-reported their RDU in the past 6 months and sexual behaviours. Age-stratified univariable associations between RDU and behaviour were examined. GBM aged 35-44 years were the most likely to report RDU, with rates decreasing with increasing age (Ptrend < 0.001). Associations between RDU and higher-risk sexual behaviours were most consistently found among GBM aged 35-54 years.
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Distribución por Edad , Uso Recreativo de Drogas/estadística & datos numéricos , Conducta Sexual/estadística & datos numéricos , Minorías Sexuales y de Género , Adulto , Anciano , Australia/epidemiología , Estudios de Cohortes , Estudios Transversales , Conductas de Riesgo para la Salud , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We aimed to compare rates of illicit drug-related hospitalisations in HIV-negative (HIV-ve) (n = 1325) and HIV-positive (HIV+ve) (n = 557) gay and bisexual men (GBM) with rates seen in the general male population and to examine the association between self-reported illicit drug use and drug-related hospitalisation. Participants were asked how often they used a range of illicit drugs in the previous 6 months at annual interviews. Drug-related hospital admissions were defined as hospital admissions for mental or behavioural disorders due to illicit drug use (ICD 10: F11-16, F18, F19), drug poisoning (T40-T45, T50) or toxic effect of gases (T53, T59, T65). Drug-related hospitalisations were 4.8 times higher in the HIV-ve cohort [SIR 4.75 (95 % CI 3.30-6.91)] and 3.5 times higher in the HIV+ve cohort [SIR 3.51 (1.92-5.88)] compared with the general population. Periods of weekly drug use [IRR 1.86 (1.01-3.46)], poly-drug use [IRR 2.17 (1.07-4.38)] and cannabis use [low use-IRR 1.95 (1.01-3.77), high use-IRR 2.58 (1.29-5.16)] were associated with drug-related hospitalisation in both cohorts, as was being a consistently high meth/amphetamine user throughout follow-up [IRR 3.24 (1.07-9.83)] and being an inconsistent or consistent injecting drug user throughout follow-up [IRR 3.94 (1.61-9.66), IRR 4.43(1.04-18.76), respectively]. Other risk factors for drug-related hospitalisation indicated the likelihood of comorbid drug and mental health issues in GBM hospitalised for drug use.
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Bisexualidad/estadística & datos numéricos , Infecciones por VIH/psicología , Seronegatividad para VIH , Seropositividad para VIH/epidemiología , Homosexualidad Masculina/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Australia/epidemiología , Estudios de Cohortes , Comorbilidad , Infecciones por VIH/epidemiología , Humanos , Drogas Ilícitas , Masculino , Metanfetamina , Persona de Mediana Edad , Factores de Riesgo , Minorías Sexuales y de Género , Trastornos Relacionados con Sustancias/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Most anal cancers are attributable to persistent human papillomavirus type 16 (HPV-16) infection. The anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), frequently regresses spontaneously. We hypothesized that T-cell responses are associated with HSIL regression. METHODS: In men who have sex with men undergoing anal cytology and high-resolution anoscopy, we measured responses to HPV-16 oncogenic proteins E6 and E7, using the CD25/CD134 assay for CD4(+) antigen-specific T cells and intracellular cytokine staining for CD4(+) and CD8(+) antigen-specific T cells. RESULTS: Of 134 participants (mean [SD] age, 51 [9.3] years; 31 [23.1%] infected with human immunodeficiency virus), 51 (38.1%) had HSIL. E6- and E7-specific CD4(+) T-cell responses were detected in 80 (59.7%) and 40 (29.9%) of the participants, respectively, and E6- and E7-specific CD8(+) T-cell responses were each detected in 25 (18.7%). HSIL was significantly associated with E7-specific CD8(+) T-cell responses (odds ratio, 4.09 [95% confidence interval, 1.55-10.77], P = .004), but not with any CD4(+) T-cell response (P ≥ .09). Twenty-six participants had HSIL a mean of 1 year before measurement of T-cell responses, and 6 (23%) of them were regressors. Five regressors (83%) had E6-specific CD4(+) T-cell responses vs 7 of 20 (35%) nonregressors (Pexact = .065). CONCLUSIONS: Systemic HPV-16 E6- and E7-specific T-cell responses were common in men who have sex with men. E6-specific CD4(+) T-cell responses may be associated with recent HSIL regression. CLINICAL TRIALS REGISTRATION: NCT02007421.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Papillomavirus Humano 16/inmunología , Infecciones por Papillomavirus/inmunología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/inmunología , Canal Anal/inmunología , Canal Anal/virología , Neoplasias del Ano/inmunología , Neoplasias del Ano/virología , Linfocitos T CD8-positivos/virología , Femenino , Homosexualidad Masculina , Humanos , Masculino , Persona de Mediana Edad , Proteínas Oncogénicas Virales/inmunología , Proteínas E7 de Papillomavirus/inmunología , Infecciones por Papillomavirus/virología , Proteínas Represoras/inmunología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/virología , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/virologíaRESUMEN
PURPOSE OF REVIEW: People are living longer and healthier lives. In recent years, there has been a focus on recognition of ongoing sexual activity among older adults and leading from this, the potential for an increase in diagnoses of sexually transmitted infections (STIs). Data on STI rates, sexual behaviour and factors affecting susceptibility to STIs are discussed. RECENT FINDINGS: There is limited published literature in this field and few recent longitudinal studies of STI acquisition in people older than 50 years. Although there is evidence of an increase in incidence, STIs remain rare in older compared with younger populations. Compared with their heterosexual counterparts, older men who have sex with men are at higher risk of incident HIV and some other STIs. The HIV epidemic is ageing as a result of increasing life span and acquisition of HIV at older ages. Improved longevity, evolving societal norms and physiological changes may place older people at risk of HIV and other STIs. SUMMARY: Routine STI screening is not warranted in all older people. Education and prevention strategies for all people at greater risk of HIV, regardless of age are required. Age-appropriate interventions designed to impart knowledge and provide the requisite skills needed to reduce STI risk in older age would be beneficial.
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Infecciones por VIH/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Anciano , Femenino , Homosexualidad Masculina , Humanos , Incidencia , Longevidad , Masculino , Persona de Mediana Edad , Factores de Riesgo , Conducta SexualRESUMEN
Vaginal preexposure prophylaxis is a promising biomedical tool for HIV prevention. Although guidelines for the clinical assessment of microbicides are available, validated markers for product safety are lacking. To inform future microbicide and multipurpose vaginal product research, we reviewed the current and past safety methods used. We searched the Cochrane, EMBASE, and Ovid MEDLINE databases for clinical studies of vaginal products for the prevention of HIV that included safety evaluations. Ninety-seven clinical studies involving 21 products were identified: 63 lasted 14 days or less, 19 were longer in duration, and 15 were effectivess studies that included also safety as an outcome. Median sample size in the safety studies was 48 participants (range, 10-799). All studies reported on urogenital endpoint, 71% included colposcopy, and 67% assessed the vaginal microflora. Markers of vaginal epithelial inflammation, systemic absorption, and systemic toxicology assessments were evaluated in 29%, 26%, and 43% of studies, respectively. Excluding the effectiveness studies, these same assessments were done before 1998 in 33%, 7%, and 27% and after 2001 in 38%, 44%, and 60% of studies, respectively. Soluble inflammatory markers were introduced after 2001. Adverse event collection was reported in 73% of studies before 1998 and in 98% after 2001. In a previous review, we recommended that larger and longer safety studies were necessary to detect clinically important toxicities and to provide assurance that agents are ready for large-scale effectiveness trials. Here, we propose a stepwise clinical assessment that can be used for future guidance.
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Fármacos Anti-VIH/uso terapéutico , Antiinfecciosos/uso terapéutico , Infecciones por VIH/prevención & control , Enfermedades de Transmisión Sexual/prevención & control , Administración Intravaginal , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Antiinfecciosos/administración & dosificación , Antiinfecciosos/efectos adversos , Biomarcadores Farmacológicos , Ensayos Clínicos como Asunto , Femenino , Infecciones por VIH/virología , Humanos , Enfermedades de Transmisión Sexual/virología , Vagina/virologíaRESUMEN
BACKGROUND: The incidence of human papillomavirus (HPV)-associated anal cancer is increasing in men who have sex with men (MSM). Screening for the presumed cancer precursor, high-grade anal squamous intraepithelial lesions (HSIL) in a manner analogous to cervical cancer screening has been proposed. Uncertainty remains regarding anal HPV natural history and the role of anal cytology and high-resolution anoscopy (HRA) as screening tests. Well-designed cohort studies are required to address these issues. METHODS/DESIGN: The SPANC study is a prospective study of the epidemiology of low-risk and high-risk anal HPV infection and related cytological and histological abnormalities in HIV-negative and HIV-positive homosexual men aged 35 years and over. The study aims to recruit 600 men from community-based settings in Sydney, Australia. There are six study visits over three years. At the first five visits men undergo a digital ano-rectal examination (DARE), an anal "Papanicolaou" (Pap) test for HPV detection, genotyping and anal cytology, followed by HRA and directed biopsy of any visible abnormalities. The men also complete a behavioural questionnaire before each visit. Questions include a detailed history of sexual behaviour, of anal symptoms, possible anal cancer risk factors and validated quality of life and psychosocial questions. Questionnaires are also completed 2 weeks and 3 months following the provision of test results and include questions on participant experience during the procedure and post-procedure symptoms, including pain and bleeding in addition to quality of life/ psychosocial outcomes. DISCUSSION: Recruitment for the study began in September 2010 and will conclude in mid-2015, with follow up continuing to 2018. Thus far, over 350 men have been recruited from a variety of community-based settings and are broadly representative of the target screening population. The SPANC study is one of only a small number of cohort studies globally to perform HPV, cytology and HRA screening on all participants over multiple time points. The study results will contribute to understanding of the natural history of anal HPV and inform the possible development of guidelines for implementing anal cancer screening programs in this population.
Asunto(s)
Canal Anal/fisiopatología , Neoplasias del Ano/prevención & control , Detección Precoz del Cáncer/psicología , Adulto , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/psicología , Carcinoma de Células Escamosas/diagnóstico , Seropositividad para VIH/complicaciones , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Nueva Gales del Sur , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Estudios Prospectivos , Calidad de Vida , Proyectos de Investigación , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Background: Gay, bisexual and other men who have sex with men (GBM) living with HIV have a substantially elevated risk of anal cancer (85 cases per 100,000 person-years vs 1-2 cases per 100,000 person-years in the general population). The precursor to anal cancer is high-grade squamous intraepithelial lesion (HSIL). Findings regarding the cost-effectiveness of HSIL screening and treatment in GBM are conflicting. Using recent data on HSIL natural history and treatment effectiveness, we aimed to improve upon earlier models. Methods: We developed a Markov cohort model populated using observational study data and published literature. Our study population was GBM living with HIV aged ≥35 years. We used a lifetime horizon and framed our model on the Australian healthcare perspective. The intervention was anal HSIL screening and treatment. Our primary outcome was the incremental cost-effectiveness ratio (ICER) as cost per quality-adjusted life-year (QALY) gained. Findings: Anal cancer incidence was estimated to decline by 44-70% following implementation of annual HSIL screening and treatment. However, for the most cost-effective screening method assessed, the ICER relative to current practice, Australian Dollar (AUD) 135,800 per QALY gained, remained higher than Australia's commonly accepted willingness-to-pay threshold of AUD 50,000 per QALY gained. In probabilistic sensitivity analyses, HSIL screening and treatment had a 20% probability of being cost-effective. When the sensitivity and specificity of HSIL screening were enhanced beyond the limits of current technology, without an increase in the cost of screening, ICERs improved but were still not cost-effective. Cost-effectiveness was achieved with a screening test that had 95% sensitivity, 95% specificity, and cost ≤ AUD 24 per test. Interpretation: Establishing highly sensitive and highly specific HSIL screening methods that cost less than currently available techniques remains a research priority. Funding: No specific funding was received for this analysis.
RESUMEN
BACKGROUND: Human immunodeficiency virus (HIV) seroadaptive behaviors, such as serosorting and strategic positioning, are being increasingly practised by homosexual men; however, their impact on sexually transmissible infections is unclear. METHODS: Participants were 1427 initially HIV-negative men enrolled from 2001 to 2004 and followed to June 2007. Participants were tested annually for anal and urethral gonorrhoea and chlamydia, herpes simplex virus, and syphilis. In addition, they reported diagnoses of these conditions, and of genital and anal warts between annual visits, and sexual risk behaviors. RESULTS: Compared with men who reported no unprotected anal intercourse (UAI), serosorting was associated with an increased risk of urethral (incidence: 6.06 vs. 3.56 per 100 person-years (PY), hazard ratio (HR) = 1.97, 95% confidence interval [CI]: 1.43-2.72) and anal (incidence 3.95 vs. 2.80 per 100 PY, HR = 1.62, 95% CI: 1.11-2.36) chlamydia. Compared with men who reported UAI with HIV nonconcordant partners, men who practised serosorting had significantly lower risk of incident syphilis (incidence 0.18 vs. 1.00 per 100 PY, HR = 0.21, 95% CI: 0.05-0.81) and urethral gonorrhoea (incidence 2.15 vs. 5.52 per 100 PY, HR = 0.61, 95% CI: 0.39-0.96). Compared with men who reported no UAI, strategic positioning was associated with an increased risk of urethral gonorrhoea (incidence 4.11 vs. 2.10 per 100 PY, HR = 1.72, 95% CI: 1.05-2.83) and chlamydia (incidence 8.71 vs. 3.56 per 100 PY, HR = 2.22, 95% CI: 1.55-3.18). Compared with men who reported receptive UAI, the incidence of anal gonorrhoea (incidence 1.48 vs. 3.83 per 100 PY, HR = 0.38, 0.20-0.74) and chlamydia (incidence 3.10 vs. 6.30 per 100 PY, HR = 0.44, 95% CI: 0.27-0.69) was significantly lower in those who practised strategic positioning. CONCLUSION: For men who reported seroadaptive behaviors, rates of some bacterial sexually transmissible infections were higher than in men who reported no UAI. However, rates were lower than for men who reported higher HIV risk behaviors.
Asunto(s)
Seronegatividad para VIH , Seroclasificación por VIH , Homosexualidad Masculina , Parejas Sexuales , Enfermedades de Transmisión Sexual/transmisión , Sexo Inseguro , Adolescente , Adulto , Anciano , Australia , Infecciones por VIH/transmisión , Seropositividad para VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Asunción de Riesgos , Conducta Sexual , Enfermedades de Transmisión Sexual/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: Anal cancer is preceded by high-risk human papillomavirus (HRHPV) infection, predominantly HPV16. No HPV assay is licenced for use in anal screening. We aimed to determine the sensitivity and specificity of four anal canal swab HPV assays to predict high-grade squamous epithelial lesions (HSIL). METHODS: In a cohort of Australian HIV-positive and negative gay and bisexual men, we compared the sensitivity and specificity of detection of 13 anal HRHPV genotypes by Linear Array (LA), Cobas 4800, EuroArray, and Anyplex II HPV28 (+ and ++ cut offs), compared their ability to predict prevalent anal HSIL, and compared anal canal HRHPV detection with HRHPV isolated from HSIL using laser capture microdissection (LCM). RESULTS: A total of 475 participants had baseline results available for all four assays (166, 35.0% HIV positive), and 169 participants had a diagnosis of cytological and/or histological HSIL. The HPV16 and any HRHPV detection were highest with Anyplex II HPV28 (+) (156, 32.8% 95% CI 28.6-37.2 and 359, 75.6%, 95% CI 71.5-79.4, respectively). For detection of concurrent HSIL and HPV16, the assay sensitivity was similar, ranging from 49.1%, 95% CI 41.4-56.9 (Anyplex II HPV28 ++) to 55.0%, 95% CI 47.2-62.7 (Anyplex II HPV28 +). For concurrent HSIL and any HRHPV detection, EuroArray was more specific than Anyplex II HPV28 (+) (45.9% 95% CI 40.2-51.7 vs 36.7%, 95% CI 31.3-42.4, p = 0.021) and had comparable specificity with Anyplex II HPV28 (++) (45.9% vs 47.2%, 95% CI 41.5-53.0, p = 0.75). All assays had high sensitivities for predicting HPV16 detected on LCM (92.5-97.5%). Anyplex II HPV28 and EuroArray were significantly more sensitive than LA for lesions caused by non-HPV16 HRHPV types on LCM. DISCUSSION: Anyplex II HPV28 and EuroArray detected more non-16 HRHPV genotypes than LA. Increasing the Anyplex II HPV28 cutoff improved specificity without compromising sensitivity for detection of concurrent HSIL.