Obstetrics and Gynaecology - Research Publications

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    Anal human papillomavirus prevalence and risk factors among men who have sex with men in Vietnam
    Tuan, LA ; Prem, K ; Pham, QD ; Toh, ZQ ; Tran, HP ; Nguyen, PD ; Mai, CTN ; Ly, LTK ; Cao, V ; Le-Ha, T-D ; Tuan, NA ; Jit, M ; Bright, K ; Brisson, M ; Nguyen, TV ; Garland, S ; Anh, DD ; Van Trang, N ; Mulholland, K (ELSEVIER SCI LTD, 2021-11)
    OBJECTIVES: Men who have sex with men (MSM) are at risk of human papillomavirus (HPV)-related cancers, while published data are scarce. This study determined HPV prevalence and risk factors in MSM in Vietnam to inform HPV prevention strategies in this key population. METHODS: A cross-sectional study of 799 MSM aged 16-50 years was conducted in Vietnam in 2017-2018. Information was collected on risk behaviours, and knowledge of HPV and anal cancer; rectal swabs were taken to detect anal HPV infection. An in-house polymerase chain reaction and Genoflow HPV array test kit were used for HPV detection and genotyping. RESULTS: The median age of the study participants was 25 years (range 18-52). Overall prevalence of any HPV and HPV16/18 infection was 32.3% and 11.0%, respectively. A higher prevalence of high-risk HPV infection to all 14 types tested was found in Ho Chi Minh City (30.9%) than in Hanoi (18.4%). High-risk HPV infection was associated with inconsistent condom use and history of engaging in sex under the influence of drugs (adjusted odds ratio (aOR), 2.27; 95% CI, 1.48-10.67), as well as having multiple sexual partners (aOR, 1.01; 95% CI, 1.00-1.02). CONCLUSIONS: High-risk anal HPV infections in Vietnamese MSM were significantly associated with risky sexual behaviours. A targeted HPV vaccination strategy would have substantial benefit for MSM in Vietnam.
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    Australia's Role in Pneumococcal and Human Papillomavirus Vaccine Evaluation in Asia-Pacific
    Toh, ZQ ; Quang, C ; Tooma, JA ; Garland, SM ; Mulholland, K ; Licciardi, PV (MDPI, 2021-08)
    Australian researchers have made substantial contributions to the field of vaccinology over many decades. Two examples of this contribution relate to pneumococcal vaccines and the human papillomavirus (HPV) vaccine, with a focus on improving access to these vaccines in low- and lower-middle-income countries (LLMICs). Many LLMICs considering introducing one or both of these vaccines into their National Immunisation Programs face significant barriers such as cost, logistics associated with vaccine delivery. These countries also often lack the resources and expertise to undertake the necessary studies to evaluate vaccine performance. This review summarizes the role of Australia in the development and/or evaluation of pneumococcal vaccines and the HPV vaccine, including the use of alternative vaccine strategies among countries situated in the Asia-Pacific region. The outcomes of these research programs have had significant global health impacts, highlighting the importance of these vaccines in preventing pneumococcal disease as well as HPV-associated diseases.
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    Editorial: Immunology of HPV Infection and Vaccination: Progress and Challenges
    Licciardi, PV ; Frazer, IH ; Garland, SM ; Mulholland, K (FRONTIERS MEDIA SA, 2021-03-12)
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    Human Papillomavirus Vaccination After COVID-19
    Toh, ZQ ; Russell, FM ; Garland, SM ; Mulholland, EK ; Patton, G ; Licciardi, P (OXFORD UNIV PRESS, 2021-04)
    The current global novel coronavirus disease 2019 (COVID-19) pandemic threatens to derail the uptake of human papillomavirus (HPV) vaccination in low- and lower-middle income countries with major disruptions to routine immunization and the introduction of new vaccines delayed. This has a major impact on the World Health Organization cervical cancer elimination strategy, where it is dependent on HPV vaccination as well as cervical cancer screening and treatment. We discuss current opportunities and barriers to achieve high uptake of HPV vaccination in low- and lower-middle income countries as well as the impact of COVID-19. Implementation of 4 key recommendations for HPV vaccination in low- and lower-middle income countries is needed: increased global financial investment; improved vaccine supply and accelerated use of a single-dose schedule; education and social marketing; and adoption of universal school-based delivery. With the commitment of the global health community, the adoption of these strategies would underpin the effective elimination of cervical cancer.
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    Cervical Cancer Prevention Through HPV Vaccination in Low- and Middle-Income Countries in Asia.
    Toh, ZQ ; Licciardi, PV ; Russell, FM ; Garland, SM ; Batmunkh, T ; Mulholland, EK ( 2017-09-27)
    Cervical cancer is ranked the first or second most common cancer in women of low- and middle-income countries (LMICs) in Asia. Cervical cancer is almost exclusively caused by human papillomavirus (HPV), and majority of the cases can be prevented with the use of HPV vaccines. The HPV vaccines have demonstrated high vaccine efficacies against HPV infection and cervical cancer precursors in clinical and post-marketing studies, and are in use in most high-income countries. However, their use in LMICs are limited mainly due to the high costs and logistics in delivering multiple doses of the vaccine. Other issues such as the safety of the vaccines, social and cultural factors, as well as poor knowledge and awareness of the virus have also contributed to the low uptake of the vaccine. This mini-review focuses on the need for HPV vaccine implementation in Asia given the substantial disease burden and underuse of HPV vaccines in LMICs in this region. In addition, the progress towards HPV vaccine introduction, and barriers preventing further rollout of these essential, life-saving vaccines are also discussed in this article.
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    Measurement of Human Papillomavirus-Specific Antibodies Using a Pseudovirion-Based ELISA Method
    Toh, ZQ ; He, L ; Chen, C ; Huang, A ; Russell, FM ; Garland, SM ; Reyburn, R ; Ratu, T ; Tuivaga, E ; Frazer, IH ; Mulholland, EK ; Licciardi, PV (FRONTIERS MEDIA SA, 2020-10-28)
    Human papillomavirus (HPV) vaccines are safe and effective in preventing HPV infection and cervical precancers. Neutralizing antibodies are thought to be the primary mechanism of protection for HPV vaccines, although the exact level required for protection has not been identified. Three common serological assays used in clinical trials to measure HPV antibodies are HPV pseudovirion-based neutralization assay (PBNA), competitive or total Luminex immunoassays (cLIA or LIA) and VLP-based enzyme linked immunosorbent assays (ELISA). While PBNA is the gold-standard for measuring neutralizing antibodies (NAb), it is labor intensive. Luminex immunoassay and VLP-ELISA are rapid and high throughput, but their reagents and equipment can be difficult to source. Nevertheless, data generated from these assays generally correlate well with PBNA. Here, we described a simplified high-throughput PsV-based ELISA for HPV antibody measurement, to circumvent some of the limitations of existing assays. Using this assay, we were able to differentiate HPV-specific IgG and IgM, and found a strong correlation between HPV-specific IgG and NAb levels, as previously determined by PBNA. This assay platform is simpler and less time-consuming than PBNA. In addition, the materials can be readily produced and obtained commercially. This assay can be used as an alternative method to measure HPV antibodies.
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    Cellular Immune Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent HPV Vaccine in Fijian Girls and Subsequent Responses to a Dose of Bivalent HPV Vaccine
    Toh, ZQ ; Cheow, KWB ; Russell, FM ; Hoe, E ; Reyburn, R ; Fong, J ; Tuivaga, E ; Ratu, FT ; Nguyen, CD ; Matanitobua, S ; Reitsma, A ; Tabrizi, SN ; Garland, SM ; Mulholland, EK ; Licciardi, PV (OXFORD UNIV PRESS INC, 2018-07)
    BACKGROUND: This study examined the cellular immunity of 0, 1, 2, and 3 doses of Gardasil vaccine (4vHPV) in girls after 6 years and their responses to a subsequent dose of Cervarix vaccine (2vHPV). METHODS: A subset of girls (n = 59) who previously received 0, 1, 2, or 3 doses of 4vHPV 6 years earlier were randomly selected from a cohort study of Fijian girls (age 15-19 years). Blood was collected before and 28 days after a dose of 2vHPV. The HPV16- and HPV18-specific cellular immune response was determined by IFNγ-ELISPOT and by measurement of cytokines in peripheral blood mononuclear cell supernatants. RESULTS: Six years after 4vHPV vaccination, HPV18-specific responses were significantly lower in the 1- (1D) or 2-dose (2D) recipients compared with 3-dose recipients (2D: IFNγ-ELISPOT: P = .008; cytokines, IFNγ: P = .002; IL-2: P = .022; TNFα: P = .016; IL-10: P = .018; 1D: IL-2: P = .031; IL-10: P = .014). These differences were no longer significant post-2vHPV. No significant differences in HPV16 responses (except IL-2, P < .05) were observed between the 2- or 1-dose recipients and 3-dose recipients. CONCLUSIONS: These data suggest that cellular immunity following reduced-dose schedules was detectable after 6 years, although the responses were variable between HPV types and dosage groups. The clinical significance of this is unknown. Further studies on the impact of reduced dose schedules are needed, particularly in high-disease burden settings.
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    HPV genoprevalence and HPV knowledge in young women in Mongolia, five years following a pilot 4vHPV vaccination campaign
    Batmunkh, T ; von Mollendorf, C ; Tulgaa, K ; Surenjav, U ; Dalmau, MT ; Namjil, N ; Tsedevdamba, B ; Tsegmed, S ; Enkhmaa, J ; Garland, SM ; Mulholland, K (ELSEVIER, 2019-12)
    BACKGROUND: In a 2012 pilot, 9111 Mongolian girls aged 11-17 years received three doses of the quadrivalent (4vHPV) vaccine, Gardasil®. This is the first study to measure early vaccine effectiveness and assess knowledge and attitudes of young women in Mongolia in relation to the human papillomavirus (HPV), the vaccine and cervical cancer. METHODS: A cohort of women vaccinated in 2012 (n = 726) and an unvaccinated cohort (n = 790) provided self-administered vaginal swabs for detection of high-risk HPV genotypes 16, 18/45, 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, 68 five years following vaccination. Participant knowledge and attitudes were assessed through a questionnaire. RESULTS: A total of 1882 questionnaires and 1516 self-administered vaginal swabs were analyzed. The prevalence of any HRHPV was 39.5% among both cohorts. The prevalence of vaccine-targeted HPV types was significantly lower in the vaccinated cohort than unvaccinated: 4.8% and 17.2% respectively. The 4vHPV was shown to be protective against HRHPV 16, 18/45 with 75% vaccine effectiveness. Participant knowledge was low. CONCLUSIONS: This study demonstrates that the 4vHPV is associated with reduced vaccine-targeted HPV detection rates in young Mongolian women. The questionnaire results highlight a need for awareness-raising initiatives in Mongolia on HPV, the vaccine and cervical cancer.
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    Recombinant human papillomavirus nonavalent vaccine in the prevention of cancers caused by human papillomavirus
    Toh, ZQ ; Kosasih, J ; Russell, FM ; Garland, SM ; Mulholland, EK ; Licciardi, P (DOVE MEDICAL PRESS LTD, 2019)
    Human papillomavirus (HPV) types 16 and 18 cause 70% of cervical cancer cases globally. The nonavalent HPV vaccine (9vHPV) was licensed in 2014 and protects against the next five most common cancer-causing HPV types (HPV 31/33/45/52/58) after HPV 16/18. Phase III clinical studies have demonstrated high vaccine efficacy (>90%) against cervical, vulvar, and vaginal precancers caused by these additional types, and have shown comparable immunogenicity to the shared genotypes to quadrivalent HPV vaccine (4vHPV). Vaccine efficacy and antibody responses for 9vHPV are found to persist for at least five years while longer-term observational studies are ongoing to monitor long-term vaccine effectiveness. The implementation of 9vHPV has the potential to prevent up to 93% of cervical cancer cases, as well as a significant proportion of other HPV-related anogenital cancers. This review article summarizes the current evidence for 9vHPV in terms of vaccine efficacy against HPV infection and related anogenital precancers, safety, and immunogenicity, as well as discussing the potential impact of this vaccine on the cervical cancer burden globally.
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    Selective Persistence of HPV Cross-Neutralising Antibodies following Reduced-Dose HPV Vaccine Schedules
    Toh, ZQ ; Kosasih, J ; Russell, FM ; Reyburn, R ; Fong, J ; Tuivaga, E ; Ratu, FT ; Nguyen, CD ; Matanitobua, S ; Do, LAH ; Menheniott, T ; Frazer, IH ; Garland, SM ; Mulholland, EK ; Licciardi, PV (MDPI, 2019-12)
    The duration of cross-neutralising antibody responses (cross-NAb) following HPV immunisation is unknown. We compared cross-NAb responses in cohort of girls who were either unimmunised or had received immunisation with one, two or three doses of 4vHPV (Gardasil®,Merck Inc.) six years earlier, before and one month after a booster dose of 2vHPV (Cervarix®, GSK). NAb to potentially cross-reactive HPV genotypes 31, 33, 45, 52 and 58 were measured using a HPV pseudovirion-based neutralisation assay. Girls who had previously received at least one dose of 4vHPV had significantly higher NAb titres for HPV31 when compared with unimmunised girls, whereas no difference in NAb titre was observed for four other genotypes (33, 45, 52 and 58). Following a single further immunisation with 2vHPV, NAb titres to each of the five tested HPV genotypes were comparable for girls who previously received one, two or three doses of 4vHPV, and were significantly higher than for previously unimmunised girls. Immunisation with one, two or three doses of 4vHPV induced NAb to HPV31 that persisted for six years, but there was no persistence of NAb to HPV33, 45, 52 or 58. Our results suggest that one or two doses of 4vHPV may provide long-term protection against HPV31.