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1.
Clin Infect Dis ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32342984

RESUMO

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.

2.
Sex Transm Infect ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341023

RESUMO

OBJECTIVE: To systematically review and appraise published data, to determine the prevalence of Mycoplasma genitalium (MG) in men who have sex with men (MSM) tested at each anatomical site, that is, at the urethra, rectum and/or pharynx. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid Medline, PubMed, Embase were searched for articles from 1st January 1981 (the year MG was first identified) to 1st June 2018. REVIEW METHODS: Studies were eligible for inclusion if they reported MG prevalence in MSM tested at the urethra, rectum and/or pharynx, in at least 50 MSM, using nucleic acid amplification testing. Data were extracted by anatomical site, symptom and HIV status. Summary estimates (95% CIs) were calculated using random-effects meta-analysis. Subgroup analyses were performed to assess heterogeneity between studies. RESULTS: Forty-six studies met inclusion criteria, with 34 reporting estimates of MG prevalence at the urethra (13 753 samples), 25 at the rectum (8629 samples) and 7 at the pharynx (1871 samples). MG prevalence was 5.0% (95% CI 3.5 to 6.8; I2=94.0) at the urethra; 6.2% (95% CI 4.6 to 8.1; I2=88.1) at the rectum and 1.0% (95% CI 0.0 to 5.1; I2=96.0) at the pharynx. The prevalence of MG was significantly higher at urethral and rectal sites in symptomatic versus asymptomatic MSM (7.1% vs 2.2%, p<0.001; and 16.1% vs 7.5%, p=0.039, respectively). MG prevalence at the urethra was significantly higher in HIV-positive compared with HIV-negative MSM (7.0% vs 3.4%, p=0.006). CONCLUSION: MG was common in MSM, particularly at urethral and rectal sites (5% to 6%). MG was more commonly detected in symptomatic men at both sites, and more common in HIV-positive men at the urethra. MG was uncommonly detected in the pharynx. Site-specific estimates are similar to those for chlamydia and will be helpful in informing testing practices in MSM. PROSPERO REGISTRATION NUMBER: CRD42017058326.

3.
J Infect Dis ; 221(6): 1017-1024, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32031634

RESUMO

BACKGROUND: The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. METHODS: To identify mutations associated with failure we sequenced key regions of the M. genitalium parC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 with failure) or doxycycline-sitafloxacin (126 patients, including 13 with failure). RESULTS: The parC G248T/S83I mutation was more common among patients with failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, P < .001) or doxycycline-sitafloxacin (50% vs 16.8%, respectively; P = .01) treatment. Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the parC mutation conferring S83I amino acid change. Treatment was more likely to fail in these infections if they had a concurrent gyrA mutation (M95I or D99N) (P = .07 for doxycycline-moxifloxacin group and P = .009 for doxycycline-sitafloxacin group), suggesting an additive effect. CONCLUSIONS: This study indicates that parC G248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and the findings will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.

4.
J Med Microbiol ; 69(2): 244-248, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31958047

RESUMO

Introduction. Mycoplasma genitalium is a sexually transmitted organism with high levels of resistance to the recommended first-line therapy, azithromycin. The ResistancePlus MG test concurrently detects M. genitalium, and the presence of macrolide-resistance mutations (MRM). European, UK and Australian guidelines recommend a diagnostic test that reports MRM to optimize treatment through resistance-guided therapy. Hence, for samples collected for use on other platforms, reflex testing using the ResistancePlus MG test would be beneficial.Aim. To validate the ResistancePlus MG assay using samples collected in Aptima buffer for testing on the Hologic Panther.Methodology. Positive (n=99) and negative (n=229) clinical samples collected in Aptima buffer were extracted on the MagNA Pure 96 (Roche Diagnostics), and tested with the ResistancePlus MG test on the LightCycler 480 II (Roche Diagnostics). Results were compared to matched samples collected using standard sample collection (urine or swab resuspended in PBS), with positive percent agreement (PPA), negative percent agreement (NPA) and Cohen's Kappa statistic.Results. The ResistancePlus MG test had high performance with a 200 µl input volume (PPA/NPA for M. genitalium detection, 92.9 % [95 % confidence interval (CI): 85.5-96.9]/100 % [95 % CI: 97.9-100], MRM detection, 96.9 % [95 % CI: 88.2-99.5]/85.7 % [95 % CI: 66.4-95.3]) and for 1 ml input volume (PPA/NPA for M. genitalium detection, 95.9%/96.6%, MRM detection, 98.4%/90.3%). Samples remained positive after storage at room temperature beyond the manufacturer-recommended storage of <60 days (mean storage time for 1 ml extraction: 129 days).Conclusion. Samples collected using Aptima collection kits are suitable for reflex testing using the ResistancePlus MG test, allowing detection of macrolide resistance.


Assuntos
Antibacterianos/farmacologia , Testes Diagnósticos de Rotina/métodos , Farmacorresistência Bacteriana , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/efeitos dos fármacos , Mycoplasma genitalium/isolamento & purificação , Austrália , Testes Diagnósticos de Rotina/instrumentação , Humanos , Macrolídeos/farmacologia , Infecções por Mycoplasma/diagnóstico , Mycoplasma genitalium/genética , Kit de Reagentes para Diagnóstico , Manejo de Espécimes
5.
Vaccine ; 38(5): 1186-1193, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31767467

RESUMO

INTRODUCTION: Australia has recently implemented major changes in cervical cancer prevention policies including introduction of primary human papillomavirus (HPV) screening starting at age 25, and replacement of the quadrivalent HPV vaccine with the nonavalent vaccine in the national school-based program. We assessed the feasibility and utility of conducting HPV testing in residual clinical specimens submitted for routine Chlamydia trachomatis screening, as a means of tracking HPV vaccine program impact among young sexually active women. METHODS: De-identified residual specimens from women aged 16-24 years submitted for chlamydia testing were collected from three pathology laboratories in Victoria and New South Wales. Limited demographic information, and chlamydia test results were also collected. Patient identifiers were sent directly from the laboratories to the National HPV Vaccination Program Register, to obtain HPV vaccination histories. Samples underwent HPV genotyping using Seegene Anyplex II HPV 28 assay. RESULTS: Between April and July 2018, 362 residual samples were collected, the majority (60.2%) of which were cervical swabs. Demographic data and vaccination histories were received for 357 (98.6%) women (mean age 21.8, SD 2.0). Overall, 65.6% of women were fully vaccinated, 9.8% partially, and 24.7% unvaccinated. The majority (86.0%) resided in a major city, 35.9% were classified in the upper quintile of socioeconomic advantage and chlamydia positivity was 7.8%.The prevalence of quadrivalent vaccine-targeted types (HPV6/11/16/18) was 2.8% (1.5-5.1%) overall with no differences by vaccination status (p = 0.729). The prevalence of additional nonavalent vaccine-targeted types (HPV31/33/45/52/58) was 19.3% (15.6-23.8%). One or more oncogenic HPV types were detected in 46.8% (95% CI 41.6-52.0%) of women. CONCLUSIONS: HPV testing of residual chlamydia specimens provides a simple, feasible method for monitoring circulating genotypes. Applied on a larger scale this method can be utilised to obtain a timely assessment of nonavalent vaccine impact among young women not yet eligible for cervical screening.

6.
Vaccine ; 37(46): 6907-6914, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31562001

RESUMO

BACKGROUND: Australia introduced a school-based human papillomavirus (HPV) vaccination program for females aged 12-13 years in 2007, with a three-year catch-up to age 26; and for boys aged 12-13 from 2013, with a two-year catch-up to age 15. This study aimed to compare the prevalence of penile HPV between teenage heterosexual males in cohorts eligible or non-eligible for the school-based male vaccination program. METHODS: Between 2014 and 2017, sexually active heterosexual males aged 17-19 were recruited from sexual health centres and community sources across Australia. Males provided a self-collected penile swab for 37 HPV genotypes using Roche Linear Array and completed a questionnaire. We calculated adjusted prevalence ratios (aPR) of HPV between males in two periods: 2014-2015 (preceding implementation of school-based male vaccination) and 2016-2017 (eligible for school-based male vaccination). Self-reported vaccine doses were confirmed with doses reported to the National HPV Vaccination Program Register. RESULTS: Overall, 152 males were recruited in 2014-2015 and 146 in 2016-2017. Numbers of female sex partners and condom use did not differ between the two periods. The prevalence of quadrivalent vaccine-preventable [4vHPV] genotypes (6/11/16/18) was low in both periods (2.6% [2014-15] versus 0.7% [2016-17]; p = 0.371; aPR 0.28 [95% CI: 0.03-2.62]). Compared with men in 2014-2015, men in 2016-2017 had a lower prevalence of any of the 37 HPV genotypes tested (21.7% versus 11.6%; aPR 0.62 [95% CI: 0.36-1.07]) and any of the 13 high-risk genotypes tested (15.8% versus 7.5%; aPR 0.59 [95% CI: 0.30-1.19]). Prevalence of low-risk HPV genotypes did not differ between the two periods. Of the males recruited in 2016-2017, 55% had received ≥1 vaccine dose. CONCLUSION: The prevalence of 4vHPV genotypes among teenage heterosexual males in both cohorts was low, presumably due to herd protection from the female-only vaccination program. Further studies are required to determine the impact of universal HPV vaccination on HPV prevalence in males.

7.
Med J Aust ; 211(3): 113-119, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31168828

RESUMO

OBJECTIVES: To report human papillomavirus (HPV) testing patterns and rates of oncogenic HPV-positivity for specimens submitted during the first 6 months after the National Cervical Screening Program switched from cytology- to primary HPV-based screening. DESIGN, PARTICIPANTS: Retrospective cross-sectional review of 195 606 specimens submitted for HPV testing, 1 December 2017 - 31 May 2018. SETTING: Large community-based general pathology laboratory in metropolitan Sydney. MAIN OUTCOME MEASURES: Prevalence of oncogenic HPV types (all, HPV16/18, non-HPV16/18) by reason for HPV test (primary screening, non-screening); for oncogenic HPV-positive women in the age band recommended for primary HPV screening (25-74 years), prevalence of cytologic abnormality and rates of 12-month follow-up and colposcopy recommendations. RESULTS: 195 606 samples were received: 157 700 (80.6%) for primary screening, 37 906 (19.4%) for non-screening tests. Oncogenic HPV was detected in 8.1% of screening tests (95% CI, 7.9-8.2%) and 20.9% of non-screening tests (95% CI, 20.5-21.3%); 35.5% (95% CI, 34.7-36.4%) of women of recommended screening age with positive oncogenic HPV screening test results also had a cytologic abnormality. The proportion of HPV16/18-positive samples with high grade abnormality was 15.3% (95% CI, 14.2-16.6%); for samples positive for other oncogenic HPV types, the proportion was 6.3% (95% CI, 5.8-6.8%). Repeat HPV testing after 12 months was recommended for 5.4% (95% CI, 5.3-5.5%) and direct colposcopy for 2.6% (95% CI, 2.5-2.7%) of screened women aged 25-74 years. CONCLUSIONS: High grade cytologic abnormalities were more common in women positive for HPV16/18, supporting their higher risk classification. Colposcopy referral rates were higher than during primary cytology-based testing, as predicted by clinical trial and modelling data. The prevalence of HPV was much higher in non-screening than in primary screening samples. Our findings indicate the renewed program is performing as expected during the initial HPV screening round.


Assuntos
Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Programas de Rastreamento/métodos , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Austrália/epidemiologia , Colposcopia , Análise Custo-Benefício , Estudos Transversais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
8.
J Clin Microbiol ; 57(9)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31243085

RESUMO

Mycoplasma genitalium is a common sexually transmitted infection with a propensity to acquire resistance to commonly used antimicrobial therapies. Bacterial load has been linked to patient symptoms and the success of treatment. In this study, we demonstrate methodology to estimate load from routine diagnostic assays using the ResistancePlus MG test (SpeeDx Pty Ltd., Australia). The method gave comparable quantitation to an M. genitalium-specific 16S rRNA quantitative PCR (qPCR; Spearman r = 0.94) for the samples analyzed (n = 499, including urine and swab types as detailed below) and was, therefore, employed to analyze typical load levels for samples in a diagnostic laboratory (total of 1,012 tests). When stratified by sample type, female urine (median, 826 genomes/ml) had the lowest load. This was significantly lower than median loads for all other sample types (male urine [6.91 × 103 genomes/ml], anal swabs [5.50 × 103], cervical swabs [8.15 × 103], endocervical swabs [3.97 × 103], and vaginal swabs [6.95 × 103]) (P < 0.0001). There were no significant differences in load estimates between the other sample types. Reproducibility of load estimates conducted on the same samples was high (r > 0.85). In conclusion, this methodology to provide load estimates for M. genitalium can be easily integrated into routine diagnostic laboratory workflow. Given the association between organism load, symptoms, and treatment success, load assessment has future diagnostic potential.

9.
Vaccine ; 37(3): 412-416, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30551987

RESUMO

Australia's transition to primary human papillomavirus (HPV) based cervical screening, has for the first time, provided a passive mechanism for monitoring the impact of vaccination on infection prevalence among women attending screening. We assessed oncogenic HPV prevalence by single year of age in the first 7  months of the program, using data collected from a large screening laboratory in Victoria, Australia, which is routinely screening using cobas 4800, cobas 6800 and Seegene assays. Among 116,052 primary screening samples from women aged 25-74, 9.25% (95%CI: 9.09-9.42%) had oncogenic HPV detected: 2.14% (95%CI: 2.05-2.22%) were 16/18 positive and 7.12% (95%CI: 6.97-7.27%) were positive for only non-16/18 HPV. Prevalence peaked at age 25-29 then decreased with age, but this was driven by non-16/18 types. HPV16/18 prevalence remained low and flat across ages, contrasting with pre-vaccination epidemiology when HPV16/18 peaked in young women. HPV-based screening can precisely monitor HPV prevalence.


Assuntos
Fatores Etários , Colo do Útero/virologia , Programas de Rastreamento/estatística & dados numéricos , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/uso terapêutico , Vacinação/estatística & dados numéricos , Adulto , Idoso , Austrália/epidemiologia , Neoplasia Intraepitelial Cervical/prevenção & controle , Neoplasia Intraepitelial Cervical/virologia , Detecção Precoce de Câncer , Feminino , Genótipo , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/prevenção & controle , Prevalência , Neoplasias do Colo do Útero/prevenção & controle
10.
J Infect Dis ; 217(10): 1590-1600, 2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29425358

RESUMO

Introduction: A quadrivalent human papillomavirus vaccination program targeting females aged 12-13 years commenced in Australia in 2007, with catch-up vaccination of 14-26 year olds through 2009. We evaluated the program's impact on HPV prevalence among women aged 18-35 in 2015. Methods: HPV prevalence among women aged 18-24 and 25-35 was compared with prevalence in these age groups in 2005-2007. For women aged 18-24, we also compared prevalence with that in a postvaccine study conducted in 2010-2012. Results: For the 2015 sample, Vaccination Register-confirmed 3-dose coverage was 53.3% (65.0% and 40.3% aged 18-24 and 25-35, respectively). Prevalence of vaccine HPV types decreased from 22.7% (2005-2007) and 7.3% (2010-2012), to 1.5% (2015) (P trend < .001) among women aged 18-24, and from 11.8% (2005-2007) to 1.1% (2015) (P = .001) among those aged 25-35. Conclusions: This study, reporting the longest surveillance follow-up to date, shows prevalence of vaccine-targeted HPV types has continued to decline among young women. A substantial fall also occurred in women aged 25-35, despite lower coverage. Strong herd protection and effectiveness of less than 3 vaccine doses likely contributed to these reductions.


Assuntos
Papillomaviridae/imunologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Adolescente , Adulto , Austrália/epidemiologia , Feminino , Humanos , Programas de Imunização/métodos , Prevalência , Vacinação/métodos , Adulto Jovem
11.
J Med Internet Res ; 19(11): e389, 2017 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-29150417

RESUMO

BACKGROUND: Young men can be difficult to engage in health research using traditional methods of recruitment. Social networking sites are increasingly being used to recruit participants into health research, due to their cost effectiveness, overall generalizability, and wide reach. OBJECTIVE: The aim of this study was to determine the feasibility of using Facebook to recruit young Australian men into a human papillomavirus (HPV) prevalence study. METHODS: We recruited male permanent residents of Australia, aged 18 to 35 years, into the HPV in Young Males (HYM) study through targeted advertising placed on Facebook. Consenting participants completed an online questionnaire and provided a self-collected penile swab for HPV DNA detection and genotyping. We compared sociodemographic characteristics of the study population with those of the general Australian male population, based on Australian 2011 census data. RESULTS: Between February 2015 and February 2017, targeted Facebook advertisements reached 1,523,239 men, resulting in 41,811 clicks through to the study website, with 1072 (2.56%) converting to lodgment of an expression of interest. Of these, 681 (63.53%) provided written informed consent and 535 (78.6% of recruited participants) completed all the study requirements. Reasons for participating in the study included altruism, past history of HPV, gaining more knowledge about HPV or the vaccine, working in the health industry, and the monetary compensation. The average advertising cost per completed study participant was Aus $48. Compared with the census population, HYM study participants were more likely to be Australian born (P<.001), be from Victoria (P=.003) or the Australian Capital Territory (P=.004), reside in a major city (P<.001), and have completed undergraduate (P<.001) or postgraduate education (P<.001). HYM study participants were less likely to report being a current smoker (P=.03), but were more likely to identify as bisexual or homosexual (294/529, 55.6%, P<.001), than the general population. CONCLUSIONS: Using Facebook is a feasible and efficient strategy for the recruitment of men from across Australia for HPV testing. This method could be used for monitoring the impact of HPV vaccination. Additional targeting may achieve a sample that is broadly demographically representative of the Australian population. Future research should explore how the sexual risk behavior characteristics of populations recruited through Facebook compare with those of traditional recruitment methods.


Assuntos
Papillomaviridae/metabolismo , Infecções por Papillomavirus/prevenção & controle , Mídias Sociais/estatística & dados numéricos , Adolescente , Adulto , Austrália , Estudos Transversais , Humanos , Masculino , Comportamento Sexual , Rede Social , Inquéritos e Questionários , Adulto Jovem
12.
Papillomavirus Res ; 4: 79-84, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29179874

RESUMO

PURPOSE: To compare human papillomavirus genotype-specific performance of two genotyping assays, Anyplex II HPV28 (Seegene) and EuroArray HPV (EuroImmun), with Linear Array HPV (Roche). METHODS: DNA extracted from clinican-collected cervical brush specimens in PreservCyt medium (Hologic), from 403 women undergoing management for detected cytological abnormalities, was tested on the three assays. Genotype-specific agreement were assessed by Cohen's kappa statistic and Fisher's z-test of significance between proportions. RESULTS: Agreement between Linear Array and the other 2 assays was substantial to almost perfect (κ = 0.60 - 1.00) for most genotypes, and was almost perfect (κ = 0.81 - 0.98) for almost all high-risk genotypes. Linear Array overall detected most genotypes more frequently, however this was only statistically significant for HPV51 (EuroArray; p = 0.0497), HPV52 (Anyplex II; p = 0.039) and HPV61 (Anyplex II; p=0.047). EuroArray detected signficantly more HPV26 (p = 0.002) and Anyplex II detected more HPV42 (p = 0.035) than Linear Array. Each assay performed differently for HPV68 detection: EuroArray and LA were in moderate to substantial agreement with Anyplex II (κ = 0.46 and 0.62, respectively), but were in poor disagreement with each other (κ = -0.01). CONCLUSIONS: EuroArray and Anyplex II had similar sensitivity to Linear Array for most high-risk genotypes, with slightly lower sensitivity for HPV 51 or 52.


Assuntos
Colo do Útero/virologia , Genótipo , Técnicas de Genotipagem/métodos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Austrália/epidemiologia , DNA Viral/genética , Feminino , Humanos , Técnicas de Diagnóstico Molecular/métodos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Reação em Cadeia da Polimerase , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade
13.
Papillomavirus Res ; 3: 80-84, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28720461

RESUMO

OBJECTIVE: HPV causes ~90% of anal cancer and HPV16 is the type most commonly associated with anal cancer. Gay and bisexual men (GBM) are at greatly increased risk. We investigated patterns of vaccine-preventable anal HPV in older GBM. METHODS: The Study of the Prevention of Anal Cancer (SPANC) is an ongoing, prospective cohort study of HIV-positive and HIV-negative Australian GBM. Participants completed questionnaires and underwent an anal swab for HPV genotyping using Roche Linear Array. We analysed baseline data from SPANC by HPV type, mean number of types, stratified by age and HIV status. RESULTS: Anal HPV results from 606 (98.2%) of 617 participants (median age 49 years, 35.7% HIV-positive) showed 525 (86.7%) had ≥1 HPV type and 178 (29.4%) had HPV16. Over one third of participants (214, 35.3%) had no nonavalent vaccine-preventable types detected. Two (0.3%) participants had all quadrivalent types and none had all nonavalent vaccine types. HIV-positive participants (p<0.001) and younger participants (p=0.059) were more likely to have more vaccine-preventable HPV types detected. CONCLUSION: Anal HPV was highly prevalent in this largely community-based GBM cohort. Vaccine-preventable HPV16 was detected in approximately one third of participants. These findings suggest that the potential efficacy of HPV vaccination of older GBM should be explored.

15.
AIDS ; 31(9): 1303-1311, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28323757

RESUMO

BACKGROUND: We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions in gay and bisexual men (GBM) in Sydney, Australia. DESIGN: Baseline analysis of a 3-year cohort study. METHODS: The Study of the Prevention of Anal Cancer is natural history study of anal HPV infection in GBM aged at least 35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1) and dual cytology staining of p16/Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers. RESULTS: The median age of the 617 participants was 49 years (range: 35-79), and 35.7% were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P < 0.001 for all). High-risk HPV (HR-HPV) viral load with a 33% cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4 and 75.4 vs. 83.2%, respectively), improved specificity (68.0 and 69.4 vs. 52.4%, respectively) and lower referral rates (47.0 and 45.0 vs. 59.2%, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3 vs. 58.2%, P = 0.005). CONCLUSION: HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal high-grade squamous intraepithelial lesion with lower referrals in GBM than anal cytology.


Assuntos
Neoplasias do Ânus/diagnóstico , Biomarcadores Tumorais/análise , DNA Viral/análise , Papillomaviridae/isolamento & purificação , RNA Viral/análise , Minorias Sexuais e de Gênero , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Adulto , Idoso , Austrália , Estudos de Coortes , Testes Diagnósticos de Rotina/métodos , Feminino , Genótipo , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Sensibilidade e Especificidade , Carga Viral
16.
Lancet Infect Dis ; 17(1): 68-77, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27282422

RESUMO

BACKGROUND: Australia introduced a national quadrivalent human papillomavirus (4vHPV) vaccination programme for girls and young women in April, 2007. The HPV genotypes targeted by the female vaccine could also affect the protection afforded to heterosexual men. We examined the prevalence of 4vHPV targeted vaccine genotypes and the nine-valent HPV (9vHPV)-targeted vaccines genotypes among sexually active, predominantly unvaccinated heterosexual men from 2004 to 2015. METHODS: We did a retrospective, observational study of urine and urethral swab specimens from heterosexual men aged 25 years or younger attending the Melbourne Sexual Health Centre between July 1, 2004, and June 30, 2015, who tested positive for Chlamydia trachomatis. We extracted HPV DNA and used the PapType HPV assay to detect 14 high-risk HPV genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) and two low-risk genotypes (6 and 11). We calculated the prevalence of any HPV genotype, genotypes 6 or 11, genotypes 16 or 18, genotypes in the 4vHPV group (6, 11, 16, or 18), five additional genotypes in the 9vHPV group (31, 33, 45, 52, or 58), and non-vaccine-targeted genotypes (31, 33, 35, 39, 45, 51, 56, 58, 59, 66, or 68). FINDINGS: We obtained data between July 1, 2004, and June 30, 2015, and did the data analysis in December, 2015. Of 1764 specimens obtained, we included 1466 in our final analysis (the others were excluded because they had indeterminate results or were duplicates). The prevalence of any HPV genotype and genotypes 31, 33, 45, 52, and 58 did not change from 2004-05 to 2014-15, but we noted reductions in genotypes 6 and 11 (from 12% [95% CI 6-21%], to 3% [1-7%], ptrend=0·008), 16 and 18 (from 13% [95% CI 7-22%] to 3% [1-6%], ptrend<0·0001), and 4vHPV-targeted genotypes (from 22% [95% CI 14-33%] to 6% [3-10%], ptrend<0·0001). Prevalence of non-vaccine-targeted genotypes increased from 16% [95% CI 9-26%] to 22% [17-29%], ptrend<0·0001). In Australian-born men, 4vHPV-targeted genotype prevalence decreased from 11 of 55 [20%, 95% CI 10-33%] to two of 74 [3%, 0-11%], ptrend<0·0001); an even greater decline occurred in Australian-born men aged 21 years or younger (from four of 13 [31%, 95% CI 9-61%] to none of 25; ptrend<0·0001). Genotypes 16 and 18 decreased (adjusted prevalence ratio [PR] 0·32, 95% CI 0·14-0·74; p=0·008) but not genotypes 6 and 11 (adjusted PR 0·50, 0·16-1·56; p=0·234) in the postvaccination period among men who had arrived in Australia within 2 years from countries with a bivalent vaccine (2vHPV) programme (England, Scotland, Wales, Cook Islands, Northern Ireland, or the Netherlands), compared with the prevaccination period. No change was noted in 4vHPV genotypes in men born overseas in other countries. INTERPRETATION: The marked reduction in prevalence of 4vHPV genotypes among mainly unvaccinated Australian-born men suggests herd protection has occurred from the female vaccination programme. Additionally, the decline in genotypes 16 and 18, but not genotypes 6 and 11, among overseas-born men predominantly from countries with a 2vHPV vaccine programme suggests that these men received benefits from herd protection for genotypes 16 and 18 from their vaccinated female partners in their own countries. These reductions could translate to reductions in HPV-related malignant conditions in men, even in countries with female-only vaccination programmes. FUNDING: The Australian National Health and Medical Research Council Program.


Assuntos
Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Programas de Imunização , Papillomaviridae/classificação , Infecções por Papillomavirus/epidemiologia , Adolescente , Austrália/epidemiologia , Feminino , Genótipo , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Humanos , Masculino , Papillomaviridae/química , Papillomaviridae/imunologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Prevalência , Saúde Reprodutiva , Estudos Retrospectivos , Vacinação/estatística & dados numéricos , Adulto Jovem
17.
J Infect Dis ; 215(2): 202-208, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27815379

RESUMO

Background: In Australia, high uptake of the quadrivalent human papillomavirus (4vHPV) vaccine has led to reductions in the prevalence of human papillomavirus (HPV) genotypes 6, 11, 16, and 18 in women and girls aged ≤25 years. We evaluated the impact of the program impact on HPV prevalence in unvaccinated male subjects. Methods: Sexually active heterosexual male subjects aged 16-35 years were recruited in 2014-2016. Participants provided a self-collected penile swab sample for HPV genotyping (Roche Linear Array) and completed a demographic and risk factor questionnaire. Results: The prevalence of 4vHPV genotypes among 511 unvaccinated male subjects was significantly lower in those aged ≤25 than in those aged >25 years: 3.1% (95% confidence interval, 1.5%-5.7%) versus 13.7% (8.9%-20.1%), respectively (P < .001); adjusted prevalence ratio, 0.22 (.09-.51; P < .001). By contrast, the prevalence of high-risk HPV genotypes other than 16 and 18 remained the same across age groups: 16.8% (95% confidence interval, 12.6%-21.9%) in men aged ≤25 years and 17.9% (12.4%-25.0%) in those aged >25 years (P = .76); adjusted prevalence ratio, 0.98, (.57-1.37; P = .58). Conclusions: A 78% lower prevalence of 4vHPV genotypes was observed among younger male subjects. These data suggest that unvaccinated men may have benefited from herd protection as much as women from a female-only HPV vaccination program with high coverage.


Assuntos
Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Austrália/epidemiologia , Feminino , Heterossexualidade , Humanos , Programas de Imunização , Masculino , Papillomaviridae/genética , Pênis/virologia , Prevalência , Inquéritos e Questionários , Adulto Jovem
18.
Twin Res Hum Genet ; 20(1): 10-18, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27917752

RESUMO

BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is a necessary prerequisite for development of cervical cancer and its precursor lesion, high-grade squamous intraepithelial lesion (HSIL). However, HPV infection is not sufficient to drive this process, and genetic and environmental factors may also play a role. METHODS/DESIGN: The Cervical Cancer, Genetics and Environment Twin Study was established to investigate the environmental and genetic influences on variation in susceptibility to cervical pre-cancer in 25- to 69-year-old monozygotic (MZ) and dizygotic (DZ) twins recruited through the Australian Twin Registry. Reviews of Papanicolaou (Pap) screening histories were undertaken to identify individual women with a history of an abnormal Pap test. This was followed by detection of HPV in archival Pap smears of selected twin pairs to determine HPV persistence. Selected twin pairs also completed a detailed questionnaire on socio-demographic characteristics, sexual behavior, and HPV knowledge. In future analyses, under the assumptions of the classical twin design, case-wise concordance for persistent HPV infection and HSIL will be calculated for MZ and DZ twin pairs, and twin pairs (both MZ and DZ) who are discordant for the above outcomes will be used to assess the contributions of measured environmental risk factors. DISCUSSION: The study examines factors related to HPV persistence and development of HSIL among female MZ and DZ twins. The results will contribute to our understanding of the natural history of cervical HPV infection and the relative contributions of genetic and environmental factors in disease progression.


Assuntos
Interação Gene-Ambiente , Infecções por Papillomavirus/genética , Lesões Intraepiteliais Escamosas Cervicais/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Doenças em Gêmeos , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Lesões Intraepiteliais Escamosas Cervicais/patologia , Lesões Intraepiteliais Escamosas Cervicais/virologia , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
19.
PLoS One ; 11(8): e0161846, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27564213

RESUMO

BACKGROUND: Human papillomavirus (HPV) vaccination targets high-risk HPV16/18 that cause 70% of all cancers of the cervix. In Australia there is a fully-funded, school-based National HPV Vaccination Program which has achieved vaccine initiation rate of 82% among age-eligible females. Improving HPV vaccination rates is important in the prevention of morbidity and mortality associated with HPV-related disease. This study aimed to identify factors and barriers associated with uptake of the HPV vaccine in the Australian Program. METHODS: Between 2011 and 2014, females aged 18-25 years, living in Victoria, Australia who were offered HPV vaccination between 2007 and 2009 as part of the National HPV Vaccination Program, living in Victoria, Australia were recruited into a a young women's study examining effectiveness of the Australian National HPV Vaccination Program. Overall, 668 participants completed the recruitment survey, which collected data of participants' demographics and HPV knowledge. In 2015 these participants were invited to complete an additional supplementary survey on parental demographics and attitudes towards vaccinations. RESULTS: In 2015, 417 participants completed the supplementary survey (62% response rate). Overall, 19% of participants were unvaccinated. In multivariate analyses, HPV vaccination was significantly associated with their being born in Australia (p<0.001), having completed childhood vaccinations (p<0.001) and their parents being main decision-makers for participants' HPV vaccination (p<0.001). The main reason reported for HPV non-vaccination was parental concern about vaccine safety (43%). Compared with HPV-vaccinated participants, those unvaccinated were significantly more likely to be opposed to all vaccines, including HPV vaccines (p<0.001) and were less likely to consider vaccinating their own children with all vaccines (p = 0.033), including HPV vaccines (p<0.001). Overall, 61% of unvaccinated participants reported that a recommendation from GPs would increase HPV vaccine acceptance. CONCLUSIONS: Attitudes towards general health, vaccinations in general, as well as HPV vaccines are important in HPV vaccine uptake. Long-term monitoring of the knowledge, attitude and beliefs towards HPV vaccination in the community is critical to ensure a continued high uptake of the vaccine and success of the program.


Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Adolescente , Adulto , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 16/patogenicidade , Papillomavirus Humano 18/imunologia , Papillomavirus Humano 18/patogenicidade , Humanos , Análise Multivariada , Infecções por Papillomavirus/imunologia , Vitória , Adulto Jovem
20.
PLoS One ; 11(8): e0160673, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27529629

RESUMO

Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC) are associated with human papillomavirus (HPV). Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS) and laser capture microdissected (LCM) tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL.


Assuntos
Neoplasias do Ânus/patologia , Ilhas de CpG/genética , Metilação de DNA , DNA Viral/genética , Papillomavirus Humano 16/genética , Microdissecção e Captura a Laser , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Ânus/genética , Neoplasias do Ânus/virologia , Biópsia , Linhagem Celular Tumoral , Feminino , Papillomavirus Humano 16/fisiologia , Humanos , Gradação de Tumores , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia
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