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  1. Woo YL, Gravitt P, Khor SK, Ng CW, Saville M
    Prev Med, 2021 03;144:106294.
    PMID: 33678225 DOI: 10.1016/j.ypmed.2020.106294
    Cervical cancer remains the fourth most common cancer in women, with 85% of deaths occurring in LMICs. Despite the existence of effective vaccine and screening tools, efforts to reduce the burden of cervical cancer must be considered in the context of the social structures within the health systems of LMICs. Compounding this existing challenge is the global COVID-19 pandemic, declared in March 2020. While it is too soon to tell how health systems priorities will change as a result of COVID-19 and its impact on the cervical cancer elimination agenda, there are opportunities to strengthen cervical screening by leveraging on several trends. Many LMICs maximized the strengths of their long established community-based primary care and public health systems with expansion of surveillance systems which incorporated mobile technologies. LMICs can harness the momentum of the measures taken against COVID-19 to consolidate the efforts against cervical cancer. Self-sampling, molecular human papillomavirus (HPV) testing and digital health will shift health systems towards stronger public health and primary care networks and away from expensive hospital-based care investments. While COVID-19 will change health systems priorities in LMICs in ways that may de-prioritize cervical cancer screening, there are significant opportunities for integration into longer-term trends towards universal health coverage, self-care and digital health.
  2. Atchison S, Shilling H, Balgovind P, Machalek DA, Hawkes D, Garland SM, et al.
    J Appl Microbiol, 2021 Nov;131(5):2592-2599.
    PMID: 33942451 DOI: 10.1111/jam.15126
    AIM: Validate the Roche, MagNAPure96 (MP96) nucleic acid extraction platform for Seegene Anyplex II HPV28 (Anyplex28) detection of Human Papillomavirus.

    METHODS AND RESULTS: Comparisons were made for Anyplex28 genotyping from 115 cervical samples extracted on the Hamilton, STARlet and the MP96. Two DNA concentrations were used for the MP96, one matched for sample input to the STARlet and another 5× concentration (laboratory standard). Agreement of HPV detection was 89·8% (κ = 0·798; P = 0·007), with HPV detected in 10 more samples for the MP96. There was a high concordance of detection for any oncogenic HPV genotype (κ = 0·77; P = 0·007) and for any low-risk HPV genotype (κ = 0·85; P = 0·008). DNA extracted at laboratory standard had a lower overall agreement 85·2% (κ = 0·708; P 

  3. Keane A, Ng CW, Simms KT, Nguyen D, Woo YL, Saville M, et al.
    Int J Cancer, 2021 12 15;149(12):1997-2009.
    PMID: 34363620 DOI: 10.1002/ijc.33759
    The WHO has launched a global strategy to eliminate cervical cancer through the scale-up of human papillomavirus (HPV) vaccination, cervical screening, and cervical cancer treatment. Malaysia has achieved high-coverage HPV vaccination since 2010, but coverage of the existing cytology-based program remains low. Pilot studies found HPV self-sampling was acceptable and effective, with high follow-up rates when a digital registry was used, and recently the Malaysian Government announced plans for a national HPV-based screening program. We therefore evaluated the impact of primary HPV screening with self-collection in Malaysia in the context of Malaysia's existing vaccination program. We used the "Policy1-Cervix" modeling platform to assess health outcomes, cost-effectiveness, resource use and cervical cancer elimination timing (the year when cervical cancer rates reach four cases per 100 000 women) of implementing primary HPV testing with self-collection, assuming 70% routine-screening coverage could be achieved. Based on available data, we assumed that compliance with follow-up was 90% when a digital registry was used, but that compliance with follow-up would be 50-75% without the use of a digital registry. We found that the current vaccination program would prevent 27 000 to 32 200 cervical cancer cases and 11 700 to 14 000 deaths by 2070. HPV testing with a digital registry was cost-effective (CER = $US 6953-7549 
  4. Woo YL, Khoo SP, Gravitt P, Hawkes D, Rajasuriar R, Saville M
    Curr Oncol, 2022 Oct 02;29(10):7379-7387.
    PMID: 36290856 DOI: 10.3390/curroncol29100579
    Program ROSE (removing obstacles to cervical screening) is a primary HPV-based cervical screening program that incorporates self-sampling and digital technology, ensuring that women are linked to care. It was developed based on the principles of design thinking in the context of Malaysia. The program illustrates the importance of collaborative partnerships and addressing the multi-faceted barriers from policy changes, and infrastructure readiness to the implementation of a radically new cervical screening program in communities. The paradigm shift in cervical cancer requires a monumental and concerted effort in educating both the healthcare providers and the general public. In this short review, we highlight how Pilot Project ROSE incorporated evidence-based tools that rapidly scaled up to Program ROSE. These ideas and solutions can be adapted and adopted by other countries. Notwithstanding the impact of COVID-19, it is incumbent on countries to pave the road towards the elimination of cervical cancer with pre-existing footpaths.
  5. Saville M, Hawkes D, Keung M, Ip E, Silvers J, Sultana F, et al.
    J Clin Virol, 2020 06;127:104375.
    PMID: 32361328 DOI: 10.1016/j.jcv.2020.104375
    BACKGROUND: In the last decade, human papillomavirus (HPV) testing has been evaluated extensively for cervical screening, with studies finding increased sensitivity compared to cytology. Another advantage of HPV based-screening is the ability to test vaginal samples that can be collected by women themselves. Self-collection has the potential to extend cervical screening coverage by increasing participation rates, particularly among women who are under-screened or have never screened. This could have a significant impact on cervical cancer prevention, as the majority of invasive cervical cancer cases occur among under-screened women. Both the Netherlands and Australia have transitioned their national programs from cytology to HPV as the primary screening test and both countries include a pathway for self-collection.

    OBJECTIVES: We evaluated the relative sensitivity for HPV detection of self-collection compared with practitioner-collected cervical specimens in the context of the Australian National Cervical Screening Program (NCSP).

    STUDY DESIGN: 303 women aged ≥18 years attending a single tertiary referral centre took their own sample using a flocked-swab, and then had a practitioner-collected sample taken at colposcopy. All samples were tested at a single laboratory on the six PCR-based HPV assays which can be utilised in the NCSP; Roche cobas 4800 and cobas, Abbott RealTime, BD Onclarity, Cepheid Xpert, and Seegene Anyplex.

    RESULTS: HPV16/18 results had high observed agreement between self- and practitioner-collected samples on all assays (range: 0.94-0.99), with good agreement for non-HPV16/18 oncogenic HPV types (range: 0.64-0.73).

    CONCLUSIONS: Self-collection for HPV-based cervical screening shows good concordance and relative sensitivity when compared to practitionercollected samples across assays in the NCSP.

  6. Gómez Román R, Wang LF, Lee B, Halpin K, de Wit E, Broder CC, et al.
    mSphere, 2020 07 08;5(4).
    PMID: 32641430 DOI: 10.1128/mSphere.00602-20
    Nipah disease is listed as one of the WHO priority diseases that pose the greatest public health risk due to their epidemic potential. More than 200 experts from around the world convened in Singapore last year to mark the 20th anniversary of the first Nipah virus outbreaks in Malaysia and Singapore. Most of these experts are now involved in responding to the coronavirus disease 2019 (COVID-19) pandemic. Here, members of the Organizing Committee of the 2019 Nipah Virus International Conference review highlights from the Nipah@20 Conference and reflect on key lessons learned from Nipah that could be applied to the understanding of the COVID-19 pandemic and to preparedness against future emerging infectious diseases (EIDs) of pandemic potential.
  7. Chan HT, Keung MHT, Nguyen I, Ip ELO, Chew SM, Siler D, et al.
    J Clin Virol Plus, 2022 Aug;2(3):100079.
    PMID: 35528049 DOI: 10.1016/j.jcvp.2022.100079
    OBJECTIVES: To examine the comparative stochasticity profile of six commercial SARS-CoV-2 nucleic acid amplification tests (NAATs) and how this may affect retesting paradigms.

    METHODS: Commercial quality control (QC) material was serially diluted in viral transport media to create a panel covering 10-10,000 copies/ml. The panel was tested across six commercial NAATs. A subset of high cycle threshold results was retested on a rapid PCR assay to simulate retesting protocols commonly used to discriminate false positives.

    RESULTS: Performance beyond the LOD differed among assays, with three types of stochasticity profiles observed. The ability of the rapid PCR assay to reproduce a true weak positive specimen was restricted to its own stochastic performance at the corresponding viral concentration.

    CONCLUSION: Stochastic performance of various NAATs overlap across low viral concentrations and affect retesting outcomes. Relying on retesting alone to discriminate false positives risk missing true positives even when a more sensitive assay is deployed for confirmatory testing.

  8. Velentzis LS, Hawkes D, Caruana M, Brotherton JM, Smith MA, Roeske L, et al.
    Tumour Virus Res, 2023 Jun;15:200255.
    PMID: 36736490 DOI: 10.1016/j.tvr.2023.200255
    Australia's cervical screening program transitioned from cytology to HPV-testing with genotyping for HPV16/18 in Dec'2017. We investigated whether program data could be used to monitor HPV vaccination program impact (commenced in 2007) on HPV16/18 prevalence and compared estimates with pre-vaccination benchmark prevalence. Pre-vaccination samples (2005-2008) (n = 1933; WHINURS), from 25 to 64-year-old women had been previously analysed with Linear Array (LA). Post-vaccination samples (2013-2014) (n = 2989; Compass pilot), from 25 to 64-year-old women, were analysed by cobas 4800 (cobas), and by LA for historical comparability. Age standardised pre-vaccination HPV16/18 prevalence was 4.85% (95%CI:3.81-5.89) by LA; post-vaccination estimates were 1.67% (95%CI:1.21-2.13%) by LA, 1.49% (95%CI:1.05-1.93%) by cobas, and 1.63% (95%CI:1.17-2.08%) for cobas and LA testing of non-16/18 cobas positives (cobas/LA). Age-standardised pre-vaccination oncogenic HPV prevalence was 15.70% (95%CI:13.79-17.60%) by LA; post-vaccination estimates were 9.06% (95%CI:8.02-10.09%) by LA, 8.47% (95%CI:7.47-9.47%) by cobas and cobas/LA. Standardised rate ratios between post-vs. pre-vaccination rates were significantly different for HPV16/18, non-16/18 HPV and oncogenic HPV: 0.34 (95%CI:0.23-0.50), 0.68 (95%CI:0.55-0.84) and 0.58 (95%CI:0.48-0.69), respectively. Additional strategies (LA for all cobas positives; combined cobas and LA results on all samples) had similar results. If a single method is applied consistently, it will provide important data on relative changes in HPV prevalence following vaccination.
  9. Saville M, Sultana F, Malloy MJ, Velentzis LS, Caruana M, Ip ELO, et al.
    J Clin Microbiol, 2019 02;57(2).
    PMID: 30463896 DOI: 10.1128/JCM.01239-18
    This study demonstrates that the clinical sensitivity, specificity, and reproducibility of the novel cobas human papillomavirus (HPV) test on the cobas 6800 system for high-risk HPV types fulfills the criteria for use in population-based cervical screening. The criteria were formulated by an international consortium, using the cobas 4800 HPV test as a validated reference assay. The cobas HPV test detected over 98% of histologically confirmed cervical intraepithelial neoplasia grade 2+ (CIN2+) lesions in women age 30 years or older, with a specificity of 98.9% compared with the reference cobas 4800 test. Both the intra- and interlaboratory agreement for the cobas HPV test were 98%. The clinical performance of the cobas HPV test is comparable to those of longitudinally validated HPV assays and fulfills the criteria for its use in primary cervical screening.
  10. Velentzis LS, Egger S, Waller J, Jennett CJ, Brotherton JML, Smith MA, et al.
    Prev Med Rep, 2024 Sep;45:102849.
    PMID: 39220611 DOI: 10.1016/j.pmedr.2024.102849
    OBJECTIVE: The coronavirus pandemic impacted health-seeking behaviour and access to primary care in Australia. We investigated factors associated with intention-to-attend and attendance of cervical screening during the pandemic, mainly in Victoria, Australia.

    METHODS: We used questionnaire and attendance data (Aug 2020-Nov 2022) from Compass-PLUS, a sub-study of the Compass randomized-controlled trial of Human Papillomavirus-based vs cytology-based screening. Data was restricted to the HPV-screening arm for comparability to the national program. We investigated associations overall and for younger (25-39 years) and older (≥40 years) cohorts, between intention-to-attend/attendance, and socio-demographics, anxiety-related scores, and agreement with beliefs about screening during the pandemic (e.g. importance of screening, increased workload, working from home, risk of infection).

    RESULTS: Among 2,226 participants, positive intention to attend screening was more likely among those with a family history of cancer (p = 0.030) or living outside major cities (p = 0.024). Increased attendance was associated with increasing age (p 

  11. Mehta N, Keung MHT, Pineda E, Lynn E, Fetene D, Lee A, et al.
    Microbiol Spectr, 2024 Sep 11.
    PMID: 39258912 DOI: 10.1128/spectrum.01493-24
    This study assessed the relative clinical sensitivity and specificity, as well as reproducibility, for high-risk HPV types of the Roche cobas HPV test when processed using the Roche cobas 5800 system. The results from this study demonstrate that the cobas HPV test using the cobas 5800 system fulfils the Meijer criteria for use in population-based cervical screening. This clinical validation study also examines the clinical sensitivity and specificity based on partial genotyping, with separate detection of HPV16 and HPV18, compared with the Roche cobas 4800 HPV test, a second-generation standard comparator assay. The cobas HPV test has a relative clinical sensitivity of 1.000, when compared with the cobas 4800 HPV test to detect histologically confirmed CIN2+ lesions in woman aged 30 years or older, with a relative clinical specificity of 0.995. The general intra- and inter-laboratory agreement for the cobas HPV test on the cobas 5800 system for finding a HPV positive result were 99.1% and 99.6%, respectively.IMPORTANCEThis study demonstrates, for the first time, the clinical performance of the Roche cobas HPV test when processed using the new cobas 5800 system [cobas (5800)]. This study shows that the cobas (5800) demonstrates relative clinical sensitivity and specificity, when compared with a standard comparator HPV test, which meets the international HPV test validation requirements. Intra- and inter-laboratory reproducibility also fulfills these criteria. The current study demonstrates that the cobas (5800) can be used for primary HPV-based cervical screening on cervical specimens.
  12. Shilling H, Murray G, Brotherton JML, Hawkes D, Saville M, Sivertsen T, et al.
    Vaccine, 2020 01 29;38(5):1186-1193.
    PMID: 31767467 DOI: 10.1016/j.vaccine.2019.11.019
    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.

  13. Capeding MR, Tran NH, Hadinegoro SR, Ismail HI, Chotpitayasunondh T, Chua MN, et al.
    Lancet, 2014 Oct 11;384(9951):1358-65.
    PMID: 25018116 DOI: 10.1016/S0140-6736(14)61060-6
    An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children.
  14. Hadinegoro SR, Arredondo-García JL, Capeding MR, Deseda C, Chotpitayasunondh T, Dietze R, et al.
    N Engl J Med, 2015 Sep 24;373(13):1195-206.
    PMID: 26214039 DOI: 10.1056/NEJMoa1506223
    BACKGROUND: A candidate tetravalent dengue vaccine is being assessed in three clinical trials involving more than 35,000 children between the ages of 2 and 16 years in Asian-Pacific and Latin American countries. We report the results of long-term follow-up interim analyses and integrated efficacy analyses.
    METHODS: We are assessing the incidence of hospitalization for virologically confirmed dengue as a surrogate safety end point during follow-up in years 3 to 6 of two phase 3 trials, CYD14 and CYD15, and a phase 2b trial, CYD23/57. We estimated vaccine efficacy using pooled data from the first 25 months of CYD14 and CYD15.
    RESULTS: Follow-up data were available for 10,165 of 10,275 participants (99%) in CYD14 and 19,898 of 20,869 participants (95%) in CYD15. Data were available for 3203 of the 4002 participants (80%) in the CYD23 trial included in CYD57. During year 3 in the CYD14, CYD15, and CYD57 trials combined, hospitalization for virologically confirmed dengue occurred in 65 of 22,177 participants in the vaccine group and 39 of 11,089 participants in the control group. Pooled relative risks of hospitalization for dengue were 0.84 (95% confidence interval [CI], 0.56 to 1.24) among all participants, 1.58 (95% CI, 0.83 to 3.02) among those under the age of 9 years, and 0.50 (95% CI, 0.29 to 0.86) among those 9 years of age or older. During year 3, hospitalization for severe dengue, as defined by the independent data monitoring committee criteria, occurred in 18 of 22,177 participants in the vaccine group and 6 of 11,089 participants in the control group. Pooled rates of efficacy for symptomatic dengue during the first 25 months were 60.3% (95% CI, 55.7 to 64.5) for all participants, 65.6% (95% CI, 60.7 to 69.9) for those 9 years of age or older, and 44.6% (95% CI, 31.6 to 55.0) for those younger than 9 years of age.
    CONCLUSIONS: Although the unexplained higher incidence of hospitalization for dengue in year 3 among children younger than 9 years of age needs to be carefully monitored during long-term follow-up, the risk among children 2 to 16 years of age was lower in the vaccine group than in the control group. (Funded by Sanofi Pasteur; ClinicalTrials.gov numbers, NCT00842530, NCT01983553, NCT01373281, and NCT01374516.).
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