Obstetrics and Gynaecology - Research Publications

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    Antibody responses following incident anal and penile infection with human papillomavirus in teenage men who have sex with men
    Zou, H ; Tabrizi, SN ; Grulich, AE ; Hocking, JS ; Garland, SM ; Bradshaw, CS ; Cornall, AM ; Fairley, CK ; Chen, MY (WILEY, 2016-08-01)
    Men who have sex with men (MSM) are at risk for human papillomavirus (HPV)-related anal cancer. Few data exist on antibody responses following incident anogenital infection with HPV in teenage MSM. A cohort of 200 MSM aged 16-20 years from Melbourne, Australia were assessed at baseline, 3, 6 and 12 months. At each visit anal and penile swabs were collected for HPV DNA and serum for HPV antibodies for genotypes 6, 11, 16 and 18 (Merck's Multiplex Assays using Luminex). The main outcome, seroconversion, was defined as the detection of HPV antibodies following a negative antibody result for the same HPV type at baseline. The seroincidence rates for HPV types 6, 11, 16 and 18 were: 19 (95% CI 12-26), 7 (3-12), 4 (1-8) and 6 (3-11) per 100 person-years, respectively. Men who experienced incident anal HPV infections from types 6/11 were significantly more likely to develop serum antibodies to the same HPV type(s) than those who experienced incident anal infections from types 16/18 [73 vs. 18%, odds ratio (OR) = 15, 95% CI: 2-118]. The median time between incident anal HPV infection and seroconversion for HPV 6, 11, 16 and 18 was: 91, 38, 161 and 182 days, respectively. Antibody responses against HPV types 6/11 were significantly more likely to occur following incident anal compared with incident penile infection with HPV types 6/11 (OR = 6, 95% CI: 2-21). The likelihood of antibody responses following anogenital HPV infections depends on the HPV type and site of infection.
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    The Performance of Anal Cytology as a Screening Test for Anal HSILs in Homosexual Men
    Jin, F ; Grulich, AE ; Poynten, IM ; Hillman, RJ ; Templeton, DJ ; Law, CLH ; Farnsworth, A ; Garland, SM ; Fairley, CK ; Roberts, JM (WILEY, 2016-06)
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    Is There a Role for the ThinPrep Imaging System in Reporting Anal Cytology?
    Roberts, JM ; Jin, F ; Ekman, D ; Adams, MK ; McDonald, RL ; Thurloe, JK ; Richards, A ; Poynten, IM ; Law, C ; Fairley, CK ; Hillman, RJ ; Tabrizi, SN ; Cornall, AM ; Templeton, DJ ; Garland, SM ; Grulich, AE ; Farnsworth, A (WILEY, 2016-05)
    BACKGROUND: The ThinPrep Imaging System (TIS) is an accurate time-saving method of reading cervical ThinPrep slides in screening programs. As anal and cervical cytology are morphologically similar, TIS can potentially be used for anal cytology. We assessed the performance of TIS on anal ThinPrep slides from homosexual men in a natural history study of human papillomavirus-related anal abnormalities. METHODS: Four hundred nineteen anal cytology slides were processed by TIS and classified by a cytologist as either No further review (slide archived) or Manual review (slide requiring full manual screen). The results were compared with the original manual screening report for all slides and specifically for those screening episodes accompanied by a high-grade squamous intraepithelial lesion (HSIL) on concurrent biopsy. RESULTS: One hundred seventy six of 419 (42.0%) slides were classified as No further review, with a trend of decreasing proportions as the degree of severity of the cytological abnormality increased. Thirteen (27.7%) slides with an original unsatisfactory report were classified as No further review. Eighty two (92.1%) of those with biopsy HSIL and cytological abnormality were classified for Manual review, including all 45 (100%) with cytological HSIL. CONCLUSION: The cervical algorithm of TIS performed best on anal samples when HSIL was present both cytologically and histologically. The 27.7% unsatisfactory slides classified as No further review may indicate need for use of different criteria from cervical cytology. Because of the high prevalence of abnormalities, and hence the large proportion of slides needing manual review, the cytologist time-saving would compare unfavorably with use of TIS in cervical screening.
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    Sex is associated with the persistence of non-optimal vaginal microbiota following treatment for bacterial vaginosis: a prospective cohort study
    Ratten, LK ; Plummer, EL ; Murray, GL ; Danielewski, J ; Fairley, CK ; Garland, SM ; Hocking, JS ; Tachedjian, G ; Chow, EPF ; Bradshaw, CS ; Vodstrcil, LA (WILEY, 2021-03)
    OBJECTIVE: Determine the associations between factors and sexual practices and the composition of the vaginal microbiome (VM) of women treated for bacterial vaginosis (BV). DESIGN: Prospective cohort study. SETTING: The Melbourne Sexual Health Centre, Melbourne, Australia. POPULATION: Seventy-five reproductive-age women diagnosed with clinical BV, treated with first-line antibiotics and followed for up to 6 months. METHODS: Women self-collected vaginal swabs and completed questionnaires at enrolment, the day following antibiotics and monthly for up to 6months until BV recurrence or no BV recurrence (n = 430 specimens). Bacterial composition was determined using 16S rRNA gene amplicon sequencing. The effects of ongoing factors on VM composition (utilising 291 monthly specimens) were assessed using generalised estimating equations population-averaged models, which accounted for repeated measures within individuals. MAIN OUTCOME MEASURES: The relative abundance of vaginal bacterial taxa. RESULTS: Women who reported ongoing sex with a regular sexual partner (RSP) had a VM comprised of increased relative abundance of non-optimal BV-associated bacteria (Adjusted co-efficient [Adjusted co-eff] = 11.91, 95% CI 3.39to20.43, P = 0.006) and a decreased relative abundance of optimal, Lactobacillus species (Adjusted co-eff = -12.76, 95% CI -23.03 to -2.49, P = 0.015). A history of BV was also associated with a decreased relative abundance of Lactobacillus spp. (Adjusted co-eff = -12.35, 95% CI -22.68, P = 0.019). The relative abundance of Gardnerella, Atopobium and Sneathia spp. increased following sex with an RSP. CONCLUSIONS: Sex with an untreated RSP after BV treatment was associated with a VM comprised of non-optimal BV-associated bacteria. BV treatment approaches may need to include partner treatment if they are to achieve a sustained optimal VM associated with improved health outcomes. TWEETABLE ABSTRACT: Sex drives a return to a 'non-optimal' vaginal microbiota after antibiotics for bacterial vaginosis.
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    Increasing Macrolide and Fluoroquinolone Resistance in Mycoplasma genitalium
    Murray, GL ; Bradshaw, CS ; Bissessor, M ; Danielewski, J ; Garland, SM ; Jensen, JS ; Fairley, CK ; Tabrizi, SN (CENTERS DISEASE CONTROL, 2017-05)
    Escalating resistance to azithromycin and moxifloxacin is being reported for Mycoplasma genitalium in the Asia-Pacific region. Analyzing 140 infections, we found pretreatment fluoroquinolone-resistance mutations in parC (13.6%) and gyrA (5%). ParC S83 changes were associated with moxifloxacin failure. Combined macrolide/fluoroquinolone-resistance mutations were in 8.6% of specimens, for which recommended therapies would be ineffective.
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    Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes
    Mesher, D ; Soldan, K ; Lehtinen, M ; Beddows, S ; Brisson, M ; Brotherton, JML ; Chow, EPF ; Cummings, T ; Drolet, M ; Fairley, CK ; Garland, SM ; Kahn, JA ; Kavanagh, K ; Markowitz, L ; Pollock, KG ; Soderlund-Strand, A ; Sonnenberg, P ; Tabrizi, SN ; Tanton, C ; Unger, E ; Thomas, SL (CENTERS DISEASE CONTROL & PREVENTION, 2016-10)
    We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20-24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important.
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    The Potential of Metatranscriptomics for Identifying Screening Targets for Bacterial Vaginosis
    Twin, J ; Bradshaw, CS ; Garland, SM ; Fairley, CK ; Fethers, K ; Tabrizi, SN ; Ravel, J (PUBLIC LIBRARY SCIENCE, 2013-09-27)
    BACKGROUND: The ribosomal RNA content of a sample collected from a woman with bacterial vaginosis (BV) was analysed to determine the active microbial community, and to identify potential targets for further screening. METHODOLOGY/PRINCIPAL FINDINGS: The sample from the BV patient underwent total RNA extraction, followed by physical subtraction of human rRNA and whole transcriptome amplification. The metatranscriptome was sequenced using Roche 454 titanium chemistry. The bioinformatics pipeline MG-RAST and desktop DNA analysis platforms were utilised to analyse results. Bacteria of the genus Prevotella (predominately P. amnii) constituted 36% of the 16S rRNA reads, followed by Megasphaera (19%), Leptotrichia/Sneathia (8%) and Fusobacterium (8%). Comparison of the abundances of several bacteria to quantitative PCR (qPCR) screening of extracted DNA revealed comparable relative abundances. This suggests a correlation between what was present and transcriptionally active in this sample: however distinct differences were seen when compared to the microbiome determined by 16S rRNA gene amplicon sequencing. To assess the presence of P. amnii in a larger pool of samples, 90 sexually active women were screened using qPCR. This bacterium was found to be strongly associated with BV (P<0.001, OR 23.3 (95%CI:2.9-190.7)) among the 90 women. CONCLUSIONS/SIGNIFICANCE: This study highlighted the potential of metatranscriptomics as a tool for characterising metabolically active microbiota and identifying targets for further screening. Prevotella amnii was chosen as an example target, being the most metabolically active species present in the single patient with BV, and was found to be detected at a high concentration by qPCR in 31% of cohort with BV, with an association with both oral and penile-vaginal sex.
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    The Study of the Prevention of Anal Cancer (SPANC): design and methods of a three-year prospective cohort study
    Machalek, DA ; Grulich, AE ; Hillman, RJ ; Jin, F ; Templeton, DJ ; Tabrizi, SN ; Garland, SM ; Prestage, G ; McCaffery, K ; Howard, K ; Tong, W ; Fairley, CK ; Roberts, J ; Farnsworth, A ; Poynten, IM (BMC, 2013-10-09)
    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.
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    Automated, Computer Generated Reminders and Increased Detection of Gonorrhoea, Chlamydia and Syphilis in Men Who Have Sex with Men
    Zou, H ; Fairley, CK ; Guy, R ; Bilardi, J ; Bradshaw, CS ; Garland, SM ; Sze, JK ; Afrizal, A ; Chen, MY ; Kaul, R (PUBLIC LIBRARY SCIENCE, 2013-04-17)
    BACKGROUND: Guidelines recommend frequent screening of men who have sex with men (MSM) for sexually transmissible infections (STIs) but few interventions have demonstrated increased testing and detection of bacterial STIs among MSM in controlled studies. METHODS: We used automated text message and email reminders generated by computer assisted self-interview (CASI) to remind MSM to retest for syphilis. We compared clinic visits, STI testing and detection rates over 12 month between men receiving reminders (reminder group) and men not offered the reminders (concurrent control group). RESULTS: Men who chose 3-monthly reminders had more clinic visits (median 3 vs 1) and higher testing rates for pharyngeal gonorrhoea (67.0% vs 33.6%), rectal gonorrhoea (62.7% vs 31.1%), urethral chlamydia (67.3% vs 39.3%), rectal chlamydia (62.9% vs 31.3%), syphilis (67.0% vs 39.3%) and HIV (64.9% vs 36.7%) (all p<0.001) than concurrent controls, within 12 months after their first visit. Also, men receiving reminders had a higher combined testing rate for all the aforementioned STIs at a same visit (55.7% vs 25.5%, p<0.001) compared with concurrent controls. This association remained after adjusting for differences in characteristics between the two groups (adjusted odds ratio:1.77, 95% confidence interval:1.51-2.08). Men receiving reminders also had a higher detection rate of: rectal gonorrhoea (3.7% vs 1.2%, p = 0.001), urethral chlamydia (3.1% vs 1.4%, p = 0.027), rectal chlamydia (6.6% vs 2.8%, p<0.001), and early, latent syphilis (1.7% vs 0.4%, p = 0.008) compared with concurrent controls. CONCLUSION: This is the first study to demonstate that a fully automated reminder system using CASI was associated with increased detection of bacterial STIs among MSM.
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    The prevalence of anal human papillomavirus among young HIV negative men who have sex with men
    Zou, H ; Fairley, CK ; Hocking, JS ; Garland, SM ; Grulich, AE ; Chen, MY (BMC, 2012-12-09)
    Men who have sex with men (MSM) especially those who are HIV positive are at risk for HPV-associated anal cancer. We systematically reviewed studies with data on the prevalence of vaccine preventable anal HPV among men who have sex with men aged 25 or younger and identified 6 studies. None of these studies were specifically designed to determine the prevalence of HPV in this population. Available data, albeit limited, suggest many young MSM may not already be HPV infected. Further studies using representative sampling focused on teenage MSM are required to confirm this.