DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging.

Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea. Methylation of EPB41L3 (1-6 CpG-sites), hTERT (1-10 CpG-sites) and FAM19A4 (1-5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously. In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity]. Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%. In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.

Performance of CADM1, MAL and miR124-2 methylation as triage markers for early detection of cervical cancer in self-collected and clinician-collected samples: an exploratory observational study in Papua New Guinea.

OBJECTIVE: WHO recommends human papillomavirus (HPV) testing for cervical screening, with triage of high-risk HPV (hrHPV) positive women. However, there are limitations to effective triage for low-resource, high-burden settings, such as Papua New Guinea. In this exploratory study, we assessed the performance of host methylation as triage tools for predicting high-grade squamous intraepithelial lesions (HSIL) in self-collected and clinician-collected samples. DESIGN: Exploratory observational study. SETTING: Provincial hospital, same-day cervical screen-and-treat trial, Papua New Guinea. PARTICIPANTS: 44 hrHPV+women, with paired self/clinician-collected samples (4 squamous cell carcinomas (SCC), 19 HSIL, 4 low-grade squamous intraepithelial lesions, 17 normal). PRIMARY AND SECONDARY OUTCOME MEASURES: Methylation levels of CADM1, MAL and miR124-2 analysed by methylation-specific PCRs against the clinical endpoint of HSIL or SCC (HSIL+) measured using liquid-based-cytology/p16-Ki67 stain. RESULTS: In clinician-collected samples, MAL and miR124-2 methylation levels were significantly higher with increasing grade of disease (p=0.0046 and p<0.0015, respectively). miR124-2 was the best predictor of HSIL (area under the curve, AUC 0.819) while MAL of SCC (AUC 0.856). In self-collected samples, MAL best predicted HSIL (AUC 0.595) while miR124-2 SCC (AUC 0.812). Combined miR124-2/MAL methylation yielded sensitivity and specificity for HSIL+ of 90.5% (95% CI 69.6% to 98.8%) and 70% (95% CI 45.7% to 88.1%), respectively, in clinician-collected samples, and 81.8% (95% CI 59.7% to 94.8%) and 47.6% (95% CI 25.7% to 70.2%), respectively, in self-collected samples. miR124-2/MAL plus HPV16/HPV18 improved sensitivity for HSIL+ (95.2%, 95% CI 76.2% to 99.9%) but decreased specificity (55.0%, 95% CI 31.5% to 76.9%). CONCLUSION: miR124-2/MAL methylation is a potential triage strategy for the detection of HSIL/SCC in low-income and middle-income country.

Mycoplasma genitalium in pregnancy, including specific co-infections, is associated with lower birthweight: A prospective cohort study.

BACKGROUND: Mycoplasma genitalium infection in pregnancy is increasingly reported at similar frequencies to other sexually transmitted infections (STIs). Knowledge on its contribution to adverse pregnancy outcomes is very limited, especially relative to other STIs or bacterial vaginosis (BV). Whether M. genitalium influences birthweight remains unanswered. METHODS: Associations between birthweight and M. genitalium and other STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis) and BV in pregnancy were examined in 416 maternal-newborn pairs from a prospective cohort study in Papua New Guinea. FINDINGS: Compared to uninfected women, M. genitalium (-166.9 g, 95% confidence interval [CI]: -324.2 to -9.7 g, p = 0.038) and N. gonorrhoeae (-274.7 g, 95% CI: -561.9 to 12.5 g, p = 0.061) infections were associated with lower birthweight in an adjusted analysis. The association for C. trachomatis was less clear, and T. vaginalis and BV were not associated with lower birthweight. STI prevalence was high for M. genitalium (13.9%), N. gonorrhoeae (5.0%), and C. trachomatis (20.0%); co-infections were frequent. Larger effect sizes on birthweight occurred with co-infections of M. genitalium, N. gonorrhoeae, and/or C. trachomatis. CONCLUSION: M. genitalium is a potential contributor to lower birthweight, and co-infections appear to have a greater negative impact on birthweight. Trials examining the impact of early diagnosis and treatment of M. genitalium and other STIs in pregnancy and preconception are urgently needed. FUNDING: Funding was received from philanthropic grants, the National Health and Medical Research Council, and the Burnet Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Point-of-care testing and treatment of sexually transmitted and genital infections to improve birth outcomes in high-burden, low-resource settings (WANTAIM): a pragmatic cluster randomised crossover trial in Papua New Guinea.

BACKGROUND: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis have been associated with adverse maternal and perinatal outcomes, but there is conflicting evidence on the benefits of antenatal screening and treatment for these conditions. We aimed to determine the effect of antenatal point-of-care testing and immediate treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis on preterm birth, low birthweight, and other adverse maternal and perinatal outcomes compared with current standard of care, which included symptom-based treatment without laboratory confirmation. METHODS: In this pragmatic cluster randomised crossover trial, we enrolled women (aged ≥16 years) attending an antenatal clinic at 26 weeks' gestation or earlier (confirmed by obstetric ultrasound), living within approximately 1 h drive of a study clinic, and able to provide reliable contact details at ten primary health facilities and their catchment communities (clusters) in Papua New Guinea. Clusters were randomly allocated 1:1 to receive either the intervention or control (standard care) in the first phase of the trial. Following an interval (washout period) of 2-3 months at the end of the first phase, each cluster crossed over to the other group. Randomisation was stratified by province. Individual participants were informed about trial group allocation only after completing informed consent procedures. The primary outcome was a composite of preterm birth (livebirth before 37 weeks' gestation), low birthweight (<2500 g), or both, analysed according to the intention-to-treat population. This study is registered with ISRCTN Registry, ISRCTN37134032, and is completed. FINDINGS: Between July 26, 2017, and Aug 30, 2021, 4526 women were enrolled (2210 [63·3%] of 3492 women in the intervention group and 2316 [62·8%] of 3687 in the control group). Primary outcome data were available for 4297 (94·9%) newborn babies of 4526 women. The proportion of preterm birth, low birthweight, or both, in the intervention group, expressed as the mean of crude proportions across clusters, was 18·8% (SD 4·7%) compared with 17·8% in the control group (risk ratio [RR] 1·06, 95% CI 0·78-1·42; p=0·67). There were 1052 serious adverse events reported (566 in the intervention group and 486 in the control group) among 929 trial participants, and no differences by trial group. INTERPRETATION: Point-of-care testing and treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis did not reduce preterm birth or low birthweight compared with standard care. Within the subgroup of women with N gonorrhoeae, there was a substantial reduction in the primary outcome. FUNDING: UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; UK Medical Research Council; the Wellcome Trust; the Australian National Health and Medical Research Council; and Swiss National Science Foundation.

Access to and utilization of COVID-19 antigen rapid diagnostic tests (Ag-RDTs) among people living with HIV (PLWH): A mixed methods study from Cambodia.

Several COVID-19 antigen rapid diagnostic tests have been approved in Cambodia, but no evidence exists about the access to and utilization of these tests. This limits public health interventions to increase testing, especially among vulnerable populations such as people living with HIV (PLWH). We conducted a mixed method study among PLWH in Phnom Penh, Cambodia, between July and August 2022 to understand their current Ag-RDT access and utilization levels, as well as key barriers and drivers. We undertook a cross-sectional survey and focus group discussions among 280 and 10 PLWH, respectively, from five HIV treatment centres using a probability-proportional-to-size and simple random sampling approach. Access was defined as having received a COVID-19 Ag-RDT within the six months and utilization as having administered a COVID-19 Ag-RDT, either to oneself or to others, within the 12 months prior to the study. We calculated means, standard deviations and proportions for continuous and categorical variables, using a linear regression model with random effects to account for clustering. Additionally, we fitted a logistic model with random effects to assess factors associated with Ag-RDT access. For the qualitative data, we used thematic analyses to identify barriers/enablers of Ag-RDT access and utilization. About 35% (n = 101) of PLWH reported having had access to an Ag-RDT test in the past six months. About 11% (n = 32) of the study participants administered the Ag-RDT to themselves, 4% (n = 10) to others and 9% (n = 24) have done both, in the past 12 months. Age and education appeared to be associated with Ag-RDT access in the logistic models. Price and advice from pharmacists were commonly reported to be the main selection criteria for the brand of Ag-RDT chosen. Ag-RDTs are an important diagnostic tool for COVID-19 among PLWH in Cambodia, but familiarity of use and price could hinder better uptake, access and utilization.

"This is really something: same place, same day result, same day treatment" women's experiences of testing positive for HPV and receiving same-day treatment in Papua New Guinea: an interpretative phenomenological analysis.

INTRODUCTION: Human papillomavirus (HPV) testing is transforming cervical screening globally. The World Health Organization (WHO) now recommends same-day HPV screen-and-treat for primary cervical screening in low- and middle-income countries (LMIC) but there is a lack of evidence on women's lived experience of testing positive for oncogenic HPV and receiving same-day treatment. This study aimed to address this knowledge gap among women participating in a same-day HPV screen-and-treat (HPV S&T) program in Papua New Guinea. METHODS: As part of a larger qualitative study, this paper explores the lived experiences of 26 women who tested positive for oncogenic HPV and were treated the same day. We analysed the data using the interpretative phenomenological analysis method. All data were managed using Nvivo 12.5. RESULTS: The interpretative phenomenological analysis led to three superordinate themes: 1) facing and alleviating initial worries, (2) transforming the disclosure process, and (3) connecting to their faith. Women's experiences of the same day HPV screen-and-treat were framed by initial emotional reactions to their positive HPV test result, and having access to treatment on the same day, which helped address their worries and fears, and transformed their experience of disclosing their test result and subsequent treatment to family and friends. CONCLUSION: This study shows that, while women experience similar initial emotional reactions, undergoing same day treatment quickly resolved the women's worries, making this program highly acceptable. Overall, women's engagement in the program confirmed its high acceptability and cultural congruence, leaving women feeling empowered and hopeful about their future, and the future of all Papua New Guinea women.

No woman left behind: achieving cervical cancer elimination among women living with HIV.

Cervical cancer is the fourth most common malignancy in women of reproductive age globally. The burden of this disease is highest in low-income and middle-income countries, especially among women living with HIV. In 2018, WHO launched a global strategy to accelerate cervical cancer elimination through rapid scale-up of prophylactic vaccination, cervical screening, and treatment of precancers and cancers. This initiative was key in raising a call for action to address the stark global disparities in cervical cancer burden. However, achieving elimination of cervical cancer among women with HIV requires consideration of biological and social issues affecting this population. This Position Paper shows specific challenges and uncertainties on the way to cervical cancer elimination for women living with HIV and highlights the scarcity of evidence for the effect of interventions in this population. We argue that reaching equity of outcomes for women with HIV will require substantial advances in approaches to HPV vaccination and improved understanding of the long-term effectiveness of HPV vaccines in settings with high HIV burden cervical cancer, just as HIV, is affected by social and structural factors such as poverty, stigma, and gender discrimination, that place the elimination strategy at risk. Global efforts must, therefore, be galvanised to ensure women living with HIV have optimised interventions, given their substantial risk of this preventable malignancy.

The effect of the Xpert HIV-1 Qual test on early infant diagnosis of HIV in Myanmar and Papua New Guinea: a pragmatic, cluster-randomised, stepped-wedge, open-label trial.

BACKGROUND: Despite proven benefits for child health, coverage of early infant diagnosis of HIV remains suboptimal in many settings. We aimed to assess the effect of a point-of-care early infant diagnosis test on time-to-results communication for infants vertically exposed to HIV. METHODS: This pragmatic, cluster-randomised, stepped-wedge, open-label trial assessed the effect of the Xpert HIV-1 Qual early infant diagnosis test (Cepheid) on time-to-results communication, compared with standard care laboratory-based testing of dried blood spots using PCR. Hospitals were the unit of randomisation for one-way crossover from control to intervention phase. Each site had between 1 month and 10 months of control phase before transitioning to the intervention, with a total of 33 hospital-months in the control phase and 45 hospital-months in the intervention phase. We enrolled infants vertically exposed to HIV at six public hospitals: four in Myanmar and two in Papua New Guinea. Infants had to have mothers with confirmed HIV infection, be younger than 28 days, and required HIV testing to be eligible for enrolment. Health-care facilities providing prevention of vertical transmission services were eligible for participation. The primary outcome was communication of early infant diagnosis results to the infant's caregiver by 3 months of age, assessed by intention to treat. This completed trial was registered with the Australian and New Zealand Clinical Trials Registry, 12616000734460. FINDINGS: In Myanmar, recruitment took place between Oct 1, 2016, and June 30, 2018; in Papua New Guinea, recruitment was between Dec 1, 2016, and Aug 31, 2018. A total of 393 caregiver-infant pairs were enrolled in the study across both countries. Independent of study time, the Xpert test reduced time to early infant diagnosis results communication by 60%, compared with the standard of care (adjusted time ratio 0·40, 95% CI 0·29-0·53, p<0·0001). In the control phase, two (2%) of 102 study participants received an early infant diagnosis test result by 3 months of age compared with 214 (74%) of 291 in the intervention phase. No safety and adverse events were reported related to the diagnostic testing intervention. INTERPRETATION: This study reinforces the importance of scaling up point-of-care early infant diagnosis testing in resource-constrained and low HIV-prevalence settings, typical of the UNICEF East Asia and Pacific region. FUNDING: National Health and Medical Research Council of Australia.

Beyond patient delay, navigating structural health system barriers to timely care and treatment in a high burden TB setting in Papua New Guinea.

Tuberculosis (TB) is a major public health issue in Papua New Guinea, with incidence rates particularly high in the South Fly District of Western Province. We present three case studies, along with additional vignettes, that were derived from interviews and focus groups carried out between July 2019 and July 2020 of people living in rural areas of the remote South Fly District depicting their challenges accessing timely TB diagnosis and care; most services within the district are only offered offshore on Daru Island. The findings detail that rather than 'patient delay' attributed to poor health seeking behaviours and inadequate knowledge of TB symptoms, many people were actively trying to navigate structural barriers hindering access to and utilisation of limited local TB services. The findings highlight a fragile and fragmented health system, a lack of attention given to primary health services, and undue financial burdens placed on people living in rural and remote areas associated with costly transportation to access functioning health services. We conclude that a person-centred and effective decentralised model of TB care as outlined in health policies is imperative for equitable access to essential health care services in Papua New Guinea.

Women's acceptability of a self-collect HPV same-day screen-and-treat program in a high burden setting in the Pacific.

BACKGROUND: A field trial to evaluate a self-collect point-of-care HPV screen-and-treat (HPV S&T) program was implemented in two Well Women Clinics in Papua New Guinea (Papua New Guinea). Assessing the acceptability of a health intervention is a core element of evaluation. In this study, we examined women's acceptability of both self-collection and HPV S&T intervention in Papua New Guinea.  METHODS: Sixty-two semi-structured interviews were conducted with women who had undergone cervical screening in the same-day self-collected HPV screen-and-treat program in Madang and Western Highlands Provinces, Papua New Guinea. Data were thematically analysed using the Theoretical Framework of Acceptability (TFA) and managed using NVivo 12.5. RESULTS: Most women agreed that self-collection was transformative: it helped circumvent the culturally embarrassing pelvic examination and increased their self-efficacy, especially due to the provision of health education, instructions, and pictorial aids. The availability of same-day results, and treatment if indicated, was particularly valued by the women because it reduced the financial and temporal burden to return to the clinic for results. It also meant they did not need to wait anxiously for long periods of time for their results. Women also appreciated the support from, and expertise of, health care workers throughout the process and spoke of trust in the HPV-DNA testing technology. Most women were willing to pay for the service to ensure its sustainability and timely scale-up throughout Papua New Guinea to support access for women in harder to reach areas. CONCLUSION: This study reported very high levels of acceptability from a field trial of self-collection and HPV same-day screen-and-treat. The program was deemed culturally congruent and time efficient. This innovative cervical screening modality could be the 'solution' needed to see wider and more immediate impact and improved outcomes for women in Papua New Guinea and other high-burden, low-resource settings.

Investigating health service availability and readiness for antenatal testing and treatment for HIV and syphilis in Papua New Guinea.

BACKGROUND: Papua New Guinea (PNG) has one of the highest burdens of HIV and syphilis in pregnancy in the Asia-Pacific region. Timely and effective diagnosis can alleviate the burden of HIV and syphilis and improve maternal and newborn health. Supply-side factors related to implementation and scale up remain problematic, yet few studies have considered their impact on antenatal testing and treatment for HIV and syphilis. This study explores health service availability and readiness for antenatal HIV and/or syphilis testing and treatment in PNG. METHODS: Using data from two sources, we demonstrate health service availability and readiness. Service availability is measured at a province level as the average of three indicators: infrastructure, workforce, and antenatal clinic utilization. The readiness score comprises 28 equally weighted indicators across four domains; and is estimated for 73 health facilities. Bivariate and multivariate robust linear regressions explore associations between health facility readiness and the proportion of antenatal clinic attendees tested and treated for HIV and/or syphilis. RESULTS: Most provinces had fewer than one health facility per 10 000 population. On average, health worker density was 11 health workers per 10 000 population per province, and approximately 22% of pregnant women attended four or more antenatal clinics. Most health facilities had a composite readiness score between 51% and 75%, with urban health facilities faring better than rural ones. The multivariate regression analysis, when controlling for managing authority, catchment population, the number of clinicians employed, health facility type and residence (urban/rural) indicated a weak positive relationship between health facility readiness and the proportion of antenatal clinic attendees tested and treated for HIV and/or syphilis. CONCLUSION: This study adds to the limited evidence base for the Asia-Pacific region. There is a need to improve antenatal testing and treatment coverage for HIV and syphilis and reduce healthcare inequalities faced by rural and urban communities. Shortages of skilled health workers, tests, and medicines impede the provision of quality antenatal care. Improving service availability and health facility readiness are key to ensuring the effective provision of antenatal care interventions.

Sexual and reproductive health needs and practices of female sex workers in Papua New Guinea: findings from a biobehavioral survey Kauntim mi tu ('Count me too').

BACKGROUND: Little research has explored the sexual and reproductive health (SRH) experience of female sex workers (FSW), including girls aged < 18 years who are commercially sexually exploited (CSE), in Papua New Guinea (PNG). This paper describes the SRH history of FSW and CSE girls and factors associated with their use of moderately or highly effective contraceptive methods in three settings in PNG. METHODS: From 2016 to 2017, respondent-driven sampling (RDS) surveys were conducted among FSW and CSE girls in Port Moresby, Lae, and Mt. Hagen. FSW and CSE girls who were born female, aged ≥12 years, sold or exchanged vaginal sex in the past 6 months, spoke English or Tok Pisin, and had a valid RDS study coupon were eligible to participate. Interviews were conducted face-to-face and participants were offered rapid routine HIV and syphilis testing. Survey logistic regression procedures were used to identify factors associated with the use of moderately or highly effective contraceptive methods. Weighted data analysis was conducted. RESULTS: A total of 2901 FSW and CSE girls (Port Moresby, 673; Lae, 709; and Mt. Hagen, 709) were enrolled. The proportion using moderately or highly effective contraceptive methods was 37.7% in Port Moresby, 30.9% in Lae, and 26.5% in Mt. Hagen. After adjusting for covariates, factors significantly associated with the use of moderately or highly effective contraceptive methods in Port Moresby were being age 20-24, being married, being divorced or separated, having one or more dependent children, being away from home for more than 1 month in the last 6 months, and having tested HIV negative. No factors were significantly associated in Lae or Mt. Hagen. ANC attendance amongst FSW and CSE girls who gave birth in last 3 years was highest in Port Moresby at 91.2%. HIV testing was inconsistently and inadequately offered at ANC across the three cities. CONCLUSIONS: Kauntim mi tu provides much-needed insight into the SRH experiences of FSW and CSE girls in PNG, where their use of moderately or highly effective contraceptive methods is low. We hope to shed light on the complicated reality they face due to illegality of sex work and multitude of complex healthcare experiences.

Adverse pregnancy and birth outcomes associated with Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum: a systematic review and meta-analysis.

OBJECTIVES: Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum (genital mycoplasmas) commonly colonise the urogenital tract in pregnant women. This systematic review aims to investigate their role in adverse pregnancy and birth outcomes, alone or in combination with bacterial vaginosis (BV). METHODS: We searched Embase, Medline and CINAHL databases from January 1971 to February 2021. Eligible studies tested for any of the three genital mycoplasmas during pregnancy and reported on the primary outcome, preterm birth (PTB) and/or secondary outcomes low birth weight (LBW), premature rupture of membranes (PROM), spontaneous abortion (SA) and/or perinatal or neonatal death (PND).Two reviewers independently screened titles and abstracts, read potentially eligible full texts and extracted data. Two reviewers independently assessed risks of bias using published checklists. Random effects meta-analysis was used to estimate summary ORs (with 95% CIs and prediction intervals). Multivariable and stratified analyses were synthesised descriptively. RESULTS: Of 57/1194 included studies, 39 were from high-income countries. In meta-analysis of unadjusted ORs, M. hominis was associated with PTB (OR 1.87, 95% CI 1.49 to 2.34), PROM, LBW and PND but not SA. U. urealyticum was associated with PTB (OR 1.84, 95% CI 1.34 to 2.55), PROM, LBW, SA and PND. U. parvum was associated with PTB (1.60, 95% CI 1.12 to 2.30), PROM and SA. Nine of 57 studies reported any multivariable analysis. In two studies, analyses stratified by BV status showed that M. hominis and U. parvum were more strongly associated with PTB in the presence than in the absence of BV. The most frequent source of bias was a failure to control for confounding. CONCLUSIONS: The currently available literature does not allow conclusions about the role of mycoplasmas in adverse pregnancy and birth outcomes, alone or with coexisting BV. Future studies that consider genital mycoplasmas in the context of the vaginal microbiome are needed. PROSPERO REGISTRATION NUMBER: CRD42016050962.

Exploring Tuberculosis Riskscapes in a Papua New Guinean 'Hotspot'.

This article explores socio-spatial dimensions of risk and how they can enhance understanding of a high burden tuberculosis (TB) context in the South Fly District of Papua New Guinea. We report on select findings from a qualitative study that included 128 semi-structured in-depth interviews and 10 focus group discussions with a wide range of South Fly District community members. Using the conceptual framework of 'riskscapes' to examine emic perspectives on risk, space and practice, we map key elements of TB riskscapes on Daru Island, South Fly District, along with solutions for navigating through these riskscapes. Overcrowding, lack of water, sanitation and hygiene, as well as food insecurity and undernutrition, were identified as common elements within participants' riskscapes, that compounded upon each other to create the perception of an assemblage of risk favourable to TB transmission.

Point-of-care HPV DNA testing of self-collected specimens and same-day thermal ablation for the early detection and treatment of cervical pre-cancer in women in Papua New Guinea: a prospective, single-arm intervention trial (HPV-STAT).

BACKGROUND: WHO recommends human papillomavirus (HPV) testing and same-day treatment for cervical screening in low-income and middle-income countries (LMICs); however, few published data exist on the validity of the strategy. We aimed to evaluate the clinical performance, treatment completion rates, adverse events profile, and acceptability of a fully integrated strategy, comprising point-of-care HPV DNA testing of self-collected specimens and same-day thermal ablation, for screening of cervical cancer in women in Papua New Guinea. METHODS: HPV-STAT was a large-scale, prospective, single-arm intervention trial conducted at two clinical sites in Papua New Guinea. Cervical screening clinics with an on-site consultant gynaecologist were selected in consultation with national and provincial health authorities, church health services, and local stakeholders. Eligible participants were women aged 30-59 years attending cervical screening services at the two clinics, who were willing to comply with study procedures and able to provide written informed consent. Women self-collected vaginal specimens for point-of-care GeneXpert testing (Cepheid, Sunnyvale, CA, USA) for oncogenic HPV types. Women testing positive for HPV underwent pelvic examination followed by same-day thermal ablation or referral for gynaecology review. All HPV-positive women and a 15% random sample of HPV-negative women provided a clinician-collected cervical specimen for liquid-based cytology. The primary outcome was clinical performance (ie, sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of the strategy for the detection of high-grade squamous intraepithelial lesion (HSIL) or worse. This trial is registered with ISRCTN, ISRCTN13476702. FINDINGS: Between June 5, 2018, and Jan 6, 2020, we recruited 4285 women, 3638 (84·9%) of whom tested negative for HPV and 647 (15·1%) tested positive for one or more oncogenic HPV type. Sensitivity of the algorithm to detect HSIL or worse was 85·4% (95% CI 81·0-89·6), with specificity 89·6% (88·6-90·6), PPV 35·2% (31·6-39·0), and NPV 98·9% (98·6-99·2). Among HPV-positive women, 602 (93·0%) received same-day thermal ablation and 42 (6·5%) were referred for gynaecology review, 37 (88·1%) of whom attended. Acceptability was high among both HPV-positive and HPV-negative women. Among the 329 HPV-positive women who attended a 3-month follow-up visit, 51 (15·5%) reported mild adverse symptoms that resolved in all cases by the follow-up visit. There were no serious adverse events. INTERPRETATION: We conducted the first real-world evaluation of a fully integrated point-of-care HPV self-collect, test, and treat strategy for same-day cervical screening in a LMIC and found it to be effective, acceptable, and safe when implemented at scale in primary health-care facilities in Papua New Guinea. Our findings support the introduction and scale-up of HPV screening and treatment for the control and elimination of cervical cancer in LMICs, as recommended by WHO. FUNDING: Australian National Health and Medical Research Council.

Towards the elimination of cervical cancer in low-income and lower-middle-income countries: modelled evaluation of the effectiveness and cost-effectiveness of point-of-care HPV self-collected screening and treatment in Papua New Guinea.

INTRODUCTION: WHO has launched updated cervical screening guidelines, including provisions for primary HPV screen-and-treat. Papua New Guinea (PNG) has a high burden of cervical cancer, but no national cervical screening programme. We recently completed the first field trials of a screen-and-treat algorithm using point-of-care self-collected HPV and same-day treatment (hereafter self-collected HPV S&T) and showed this had superior clinical performance and acceptability to visual inspection of the cervix with acetic acid (VIA). We, therefore, evaluated the effectiveness, cost-effectiveness and resource implications of a national cervical screening programme using self-collected HPV S&T compared with VIA in PNG. METHODS: An extensively validated platform ('Policy1-Cervix') was calibrated to PNG. A total of 38 strategies were selected for investigation, and these incorporated variations in age ranges and screening frequencies and allowed for the identification of the optimal strategy across a wide range of possibilities. A selection of strategies that were identified as being the most effective and cost-effective were then selected for further investigation for longer-term outcomes and budget impact estimation. In the base case, we assumed primary HPV testing has a sensitivity to cervical intraepithelial neoplasia 2 (CIN2+) + of 91.8% and primary VIA of 51.5% based on our earlier field evaluation combined with evidence from the literature. We conservatively assumed HPV sampling and testing would cost US$18. Costs were estimated from a service provider perspective based on data from local field trials and local consultation. RESULTS: Self-collected HPV S&T was more effective and more cost-effective than VIA. Either twice or thrice lifetime self-collected HPV S&T would be cost-effective at 0.5× gross domestic product (GDP) per capita (incremental cost-effectiveness ratio: US$460-US$656/life-years saved; 1GDPper-capita: US$2829 or PGK9446 (year 2019)) and could prevent 33 000-42 000 cases and 23 000-29 000 deaths in PNG over the next 50 years, if scale-up reached 70% coverage from 2023. CONCLUSION: Self-collected HPV S&T was effective and cost-effective in the high-burden, low-resource setting of PNG, and, if scaled-up rapidly, could prevent over 20 000 deaths over the next 50 years. VIA screening was not effective or cost-effective. These findings support, at a country level, WHO updated cervical screening guidelines and indicate that similar approaches could be appropriate for other low-resource settings.

Adverse pregnancy and perinatal outcomes associated with Mycoplasma genitalium: systematic review and meta-analysis.

OBJECTIVE: To examine associations between Mycoplasma genitalium infection during pregnancy and adverse outcomes. METHODS: We did a systematic review of observational studies. We searched Medline, EMBASE, the Cochrane Library and CINAHL up to 11 August 2021. Studies were included if they compared preterm birth, spontaneous abortion, premature rupture of membranes, low birth weight or perinatal death between women with and without M. genitalium. Two reviewers independently assessed articles for inclusion and extracted data. We used random-effects meta-analysis to estimate summary ORs and adjusted ORs, with 95% CIs, where appropriate. Risk of bias was assessed using established checklists. RESULTS: We identified 116 records and included 10 studies. Women with M. genitalium were more likely to experience preterm birth in univariable analyses (summary unadjusted OR 1.91, 95% CI 1.29 to 2.81, I2=0%, 7 studies). The combined adjusted OR was 2.34 (95% CI 1.17 to 4.71, I2=0%, 2 studies). For spontaneous abortion, the summary unadjusted OR was 1.00 (95% CI 0.53 to 1.89, I2=0%, 6 studies). The adjusted OR in one case-control study was 0.9 (95% CI 0.2 to 3.8). Unadjusted ORs for premature rupture of membranes were 7.62 (95% CI 0.40 to 145.86, 1 study) and for low birth weight 1.07 (95% CI 0.02 to 10.39, 1 study). For perinatal death, the unadjusted OR was 1.07 (95% CI 0.49 to 2.36) in one case-control and 38.42 (95% CI 1.45 to 1021.43) in one cohort study. These two ORs were not combined, owing to heterogeneity. The greatest risk of bias was the failure in most studies to control for confounding. CONCLUSION: M. genitalium might be associated with an increased risk of preterm birth. Further prospective studies, with adequate control for confounding, are needed to understand the role of M. genitalium in adverse pregnancy outcomes. There is insufficient evidence to indicate routine testing and treatment of asymptomatic M. genitalium in pregnancy. PROSPERO REGISTRATION NUMBER: CRD42016050962.

The Prevalence of Antimicrobial Resistant Neisseria gonorrhoeae in Papua New Guinea: A Systematic Review and Meta-Analysis.

Neisseria gonorrhoeae antimicrobial resistance (NG AMR) has become an urgent concern globally. The World Health Organization, the United States of America Centers for Disease Control, and other regulators have called to improve resistance-testing methods to enhance NG AMR surveillance. NG AMR surveillance remains critical in informing treatment; unfortunately, this is often lacking in settings with limited resources, such as Papua New Guinea (PNG). We conducted a systematic review and a prevalence meta-analysis, and provided an overview of NG AMR in PNG. We showed the lack of NG AMR data in the last decade, and emphasized the need for NG AMR surveillance in PNG. Since NG AMR testing by the NG culture method is unreliable in PNG, we suggested using molecular tests to complement and enhance NG AMR surveillance.

A socio-ecological analysis of factors influencing HIV treatment initiation and adherence among key populations in Papua New Guinea.

BACKGROUND: In Papua New Guinea (PNG) members of key populations, including female sex workers (FSW), men who have sex with men (MSM) and transgender women (TGW), have higher rates of HIV compared to the general adult population and low engagement in HIV care. This paper examines the socio-ecological factors that encourage or hinder HIV treatment initiation and adherence among HIV positive members of key populations in PNG. METHODS: As part of a larger biobehavioural survey of key populations in PNG, 111 semi-structured interviews were conducted with FSW, MSM and TGW, of whom 28 identified as living with HIV. Interviews from 28 HIV positive participants are used in this analysis of the influences that enabled or inhibited HIV treatment initiation and treatment adherence. RESULTS: Enablers included awareness of the biomedical benefits of treatment; experiences of the social, familial and health benefits of early treatment initiation and adherence; support provided by family and friends; and non-judgmental and supportive HIV service provision. Factors that inhibited treatment initiation and adherence included perception of good health and denial of HIV diagnosis; poor family support following positive diagnosis; and anonymity and stigma concerns in HIV care services. CONCLUSION: Exploring health promotion messages that highlight the positive health impacts of early treatment initiation and adherence; providing client-friendly services and community-based treatment initiation and supply; and rolling out HIV viral load testing across the country could improve health outcomes for these key populations.