Obstetrics and Gynaecology - Research Publications
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ItemLooking beyond human papillomavirus (HPV) genotype 16 and 18: Defining HPV genotype distribution in cervical cancers in Australia prior to vaccination(WILEY, 2017-10-15)Australia has implemented a high-coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser-capture microdissection. Archived FFPE tissue was reviewed by specialist pathologists, sandwich sectioned, and initially whole-tissue sections genotyped for HPV. Samples were first genotyped using SPF10-LiPA25 (version 1). Negative samples were screened with DNA ELISA kit HPV SPF10, followed by genotyping with SPF+ LiPA if ELISA positive. If still negative, samples were tested on a qPCR assay targeting the E6 region of HPV16, 18, 45 and 33. Of the 847 cancers (65.1% squamous, 28.7% adenocarcinoma, 4.3% adenosquamous, 2.0% other), 92.9% had HPV detected. Of the HPV-positive cancers, 607 of 787 (77.1%) contained HPV16 or 18, 125 of 787 (15.9%) contained HPV31/33/45/52 or 58, and 55 (7.0%) another HPV type. There was a strong correlation between HPV type and age, with younger women most likely to have HPV16/18 detected and least likely HPV negative. Our findings indicate that cervical cancers diagnosed in Australia more frequently contain HPV16/18 than in international series. This could be due to cervical screening in Australia increasing the proportion of adenocarcinomas, in which types 18 and 16 more strongly predominate, due to prevention of squamous cancers.
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ItemAntibody responses following incident anal and penile infection with human papillomavirus in teenage men who have sex with men(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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ItemA case series of young women with spontaneous regression of vulval intraepithelial neoplasia: Demographics and associated HPV genotypes(WILEY, 2016-06)OBJECTIVE: To review the clinical features, demography and human papillomavirus (HPV) genotype in a group of young women with usual type vulval intraepithelial neoplasia (VIN) whose lesions regressed spontaneously. MATERIALS AND METHODS: A retrospective case note review was made of the records of women with a diagnosis of usual type VIN whose lesions resolved spontaneously. The clinical features, demography, associated conditions, time to regression and follow-up data were extracted. Stored paraffin-embedded biopsy tissue was tested for the presence and genotype of HPV. RESULTS: Fifty-four women were identified. The median age at diagnosis was 19 years. Forty-four women (81%) were of non-European ethnicity. The median time to regression was 9 months. In 44 (81%) cases, the lesion was an incidental finding during clinical examination. The majority of lesions were multifocal and pigmented (44 (81%) and 48 (89%), respectively). HPV was detected in 40 (87%) of the 46 available biopsy samples, and HPV genotype 16 was identified in 33 (82.5%). Recurrences of usual type VIN occurred in three women, and these all resolved spontaneously. CONCLUSION: Women diagnosed with usual type VIN which resolves spontaneously are very young, mainly non-European, and usually present with multiple, asymptomatic pigmented lesions. HPV genotypes and their frequencies are similar to those detected in older women with usual type VIN. This clinically defined group of women may be managed by observation alone if follow-up is assured.
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ItemIs There a Role for the ThinPrep Imaging System in Reporting Anal Cytology?(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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ItemPostnatal probiotics and allergic disease in very preterm infants: Sub-study to the ProPrems randomized trial(WILEY, 2020-01)BACKGROUND: Probiotic supplementation to mothers and/or their term-born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants. METHODS: This sub-study was an a priori secondary outcome of the ProPrems multi-center, double-blind, placebo-controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens. RESULTS: There was no difference in eczema incidence between the probiotic and placebo groups (35[30%] of 118 infants vs 37[27%] of 137 infants, respectively, absolute difference 2.65%, 95% CI -8.45 to 13.75). Similarly, the incidence of atopic eczema (6[5%] of 118 vs 3[2%] of 137), food allergy (4[3%] of 124 vs 2[1%] of 154), wheeze (39[31%] of 127 vs 45[29%] of 154), and atopic sensitization (14[13%] of 106 vs 13[11%] of 123) were similar between the probiotic and placebo groups. CONCLUSION: This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed.
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ItemAssociation between visual inspection of the cervix with acetic acid examination and high-risk human papillomavirus infection, Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in Papua New Guinea(WILEY, 2018-10)BACKGROUND: Papua New Guinea (PNG) has among the highest estimated burdens of cervical cancer globally but currently has no national cervical screening program. Visual inspection of the cervix with acetic acid (VIA) is a low-cost screening strategy endorsed by the World Health Organization that has been adopted in many low-resource settings but not previously evaluated in PNG. AIM: To evaluate the association between VIA examination findings and high-risk HPV (hrHPV) infection; and the impact of concomitant genital Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis on the interpretation of VIA findings. METHODS: A prospective clinical cohort study among women aged 30-59 years attending Well Woman Clinics in PNG. Main outcome measures were VIA examination findings and laboratory-confirmed hrHPV, C. trachomatis, N. gonorrhoeae and T. vaginalis. RESULTS: A total of 614 women were enrolled, of whom 87.5% (537/614) underwent VIA, and 12.5% (77/614) did not due to pre-existing cervicitis or inability to visualise the transformation zone. Among the 537 women who underwent VIA, 21.6% were VIA positive, 63.7% VIA negative, and 14.7% had indeterminate findings. The prevalence of hrHPV infection (n = 614) was 14.7%; C. trachomatis, 7.5%; N. gonorrhoeae, 8.0%; and T. vaginalis, 15.0%. VIA positive women were more likely to have HPV16 (odds ratio: 5.0; 95%CI: 1.6-15.6; P = 0.006) but there was no association between HPV18/45, all hrHPV types (combined), C. trachomatis, N. gonorrhoeae or T. vaginalis. CONCLUSIONS: VIA positivity was associated with HPV16, but not with other hrHPV infections, nor with genital C. trachomatis, N. gonorrhoeae or T. vaginalis in this setting.
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ItemPoint-of-care testing and treatment of sexually transmitted infections to improve birth outcomes in high-burden, low-income settings: Study protocol for a cluster randomized crossover trial (the WANTAIM Trial, Papua New Guinea)(F1000 Research Ltd, 2019-03-22)Background: Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis and bacterial vaginosis have been associated with preterm birth and low birth weight, and are highly prevalent among pregnant women in many low- and middle-income settings. There is conflicting evidence on the potential benefits of screening and treating these infections in pregnancy. Newly available diagnostic technologies make it possible, for the first time, to conduct definitive field trials to fill this knowledge gap. The primary aim of this study is to evaluate whether antenatal point-of-care testing and immediate treatment of these curable sexually transmitted and genital infections (STIs) leads to reduction in preterm birth and low birth weight. Methods : The Women and Newborn Trial of Antenatal Interventions and Management (WANTAIM) is a cluster-randomised crossover trial in Papua New Guinea to compare point-of-care STI testing and immediate treatment with standard antenatal care (which includes the WHO-endorsed STI ‘syndromic’ management strategy based on clinical features alone without laboratory confirmation). The unit of randomisation is a primary health care facility and its catchment communities. The primary outcome is a composite measure of two events: the proportion of women and their newborns in each trial arm, who experience either preterm birth (delivery <37 completed weeks of gestation as determined by ultrasound) and/or low birth weight (<2500 g measured within 72 hours of birth). The trial will also evaluate neonatal outcomes, as well as the cost-effectiveness, acceptability and health system requirements of this strategy, compared with standard care. Conclusions: WANTAIM is the first randomised trial to evaluate the effectiveness, cost-effectiveness, acceptability and health system requirements of point-of-care STI testing and treatment to improve birth outcomes in high-burden settings. If the intervention is proven to have an impact, the trial will hasten access to these technologies and could improve maternal and neonatal health in high-burden settings worldwide. Registration: ISRCTN37134032 .
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ItemMycoplasma genitalium in the Far North Queensland backpacker population: An observational study of prevalence and azithromycin resistance(PUBLIC LIBRARY SCIENCE, 2018-08-28)BACKGROUND: Mycoplasma genitalium is a sexually transmitted infection (STI), and a common cause of non-gonococcal urethritis (NGU). There is concern regarding the rise in prevalence of M. genitalium and rates of resistance to macrolide antibiotics. International backpackers represent a unique population that may be at an increased risk of STIs. The purpose of this study was to determine the prevalence of M. genitalium and antibiotic resistance in international backpackers. METHODS: First void urine samples were obtained utilising opportunistic sampling from 294 non-treatment-seeking international backpackers at a variety of hostels in Cairns, Queensland Australia. Participants also answered a fixed-answer survey regarding sociodemographic characteristics and sexual risk behaviours. Samples were tested for M. genitalium, Chlamydia trachomatis and Neisseria gonorrhoeae using polymerase chain reaction (PCR). Samples positive for M. genitalium were investigated for macrolide resistance-associated mutations in the 23S rRNA genome at positions A2058G, A2058C, A2058T, A2059G and A2059C (Escherichia coli numbering). RESULTS: Of the 294 samples, 23 failed the internal control. The prevalence of M. genitalium was 1.8% (5/271, 95% confidence interval [CI] ± 1.58), C. trachomatis was 4.1% (11/271, 95% CI ± 2.36) and N. gonorrhoeae was not detected. Macrolide resistance-associated mutations were identified in 40% (2/5) of M. genitalium-positive samples. M. genitalium infection was associated with reporting symptoms (odds ratio [OR] 14.36, 95% CI 2.17-94.94, p < 0.05). CONCLUSIONS: M. genitalium and C. trachomatis are relatively common amongst non-treatment seeking international backpackers, but may not differ from Australian population prevalence. This article provides evidence to further support the increased utilisation of M. genitalium PCR in the diagnosis of NGU, and for macrolide resistance testing for all identified M. genitalium infections.
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ItemTelomerase activity in cervical scrapes of women with high-grade cervical disease: A nested case-control study(SPANDIDOS PUBL LTD, 2018-01)Epidemiological information on telomerase activity (TA) and development of cervical lesions is scarce. A nested case-control study was carried out within a cohort of Colombian women tested for Human Papillomavirus (HPV). Measurement of TA was done in cervical scrapes of 25 women who developed High Grade Squamous Intraepithelial Lesion (HGSIL) during the first 6 years of follow-up and was compared with that of 104 control women who maintained normal cytology during the entire follow-up. TA was measured by a telomerase repeat amplification protocol-ELISA. TA and HPV infections were significantly more frequent in cases than in controls. Likewise, 68% of the cases were positive for both TA and HPV compared with only 7.7% of the controls (P<0.0001). Factors independently associated with increased odds of HGSIL included TA, high risk HPV (hrHPV) infections and multiple parities. When restricted to hrHPV positive women, TA was strongly associated with increased odds of HGSIL (adjusted odds ratio=37.94, 95% confidence interval, 1.64-678.1). In addition to an infection with hrHPV, TA appears to be a significant cofactor for HGSIL.