A comparison of ThinPrep against four non-volatile transport media for HPV testing at or near the point of care.

The Xpert HPV Test is used at point of care for cervical screening in a number of low and middle income countries (LMIC). It is validated for use with ThinPrep-PreservCyt transport medium which has a high methanol content and is therefore classified as a dangerous good for shipping, making cost, transportation and use challenging within LMIC. We compared the performance of ThinPrep against four non-volatile commercially available media for human papillomavirus (HPV) point of care testing. Ten-fold serial dilutions were prepared using three HPV cell lines each positive for 16, 18 or 31 and with each suspended in five different media types. The media types consisted of Phosphate Buffered Saline (ThermoFisher Scientific, USA), Sigma Virocult (Medical Wire and Equipment, UK), MSwab (Copan, Italy) Xpert Transport Media (Cepheid, USA) and ThinPrep-PreservCyt (Hologic, USA). A total of 105 Xpert HPV tests were conducted in a laboratory setting, with seven 10-fold dilutions of each of the three HPV genotypes tested in all five media types. The lowest HPV 10-fold dilution detected for any media, or cell line was the fifth dilution. MSwab was the only medium to detect HPV to the fifth dilution across all three cell types. MSwab transport media may be a suitable alternative to ThinPrep for Xpert HPV point of care testing. A field based, head to head comparison of both media types using the Xpert HPV assay is warranted to confirm these laboratory based findings.

PERPETRATION OF VIOLENCE BY FEMALE SEX WORKERS IN PAPUA NEW GUINEA: 'WE WILL CRUSH THEIR BONES'.

There is a small but important body of literature on female sex workers' (FSWs) violence towards others, but little of that focused on low- and middle-income countries. Drawn from a larger biobehavioural study of FSWs in three cities in Papua New Guinea, we analyse the interviews from 19 FSWs who reported having perpetrated physical violence towards four major groups: (1) ex-husbands; (2) clients; (3) other sex workers and (4) other people (mainly women). Our study demonstrates that FSWs' use of violence arises from a complex set of social, material and gendered circumstances and cannot be addressed in isolation from other aspects of their lives.

Evaluation of p16/Ki-67 dual-stain cytology performed on self-collected vaginal and clinician-collected cervical specimens for the detection of cervical pre-cancer.

OBJECTIVES: To compare the performance of dual immunostaining of p16INK4a and Ki-67 proteins performed on self-collected vaginal specimens and clinician-collected cervical specimens, and to evaluate the performance of this technique in predicting high-grade disease. METHODS: Women aged 30-59 years (n = 1005) were recruited at two well-women clinics in Papua New Guinea. Each woman provided both cervical and vaginal specimens that were tested for high-risk human papillomavirus (hrHPV) DNA using the Xpert HPV Test (Cepheid) at point of care. A subset of paired cervical and vaginal specimens (n = 243) were selected to undergo CINTec® PLUS (Roche) p16/Ki-67 dual-stain cytology and liquid-based cytology (LBC). RESULTS: Fifty-five pairs (22%) were excluded from further analysis because the smears were not assessable. Of the 189 remaining paired specimens, 74 pairs (39.1%) were positive for one or more hrHPV genotypes. When comparing results of the dual stain, the overall percent agreement, positive and negative percent agreements and κ value between the cervical and vaginal specimens were 87.8% (CI 82.3-92.1%), 64.6% (CI 49.5-77.8%), 95.7% (CI 91.0-98.0%) and 0.65 (CI 0.51-0.79%) respectively. The sensitivity of the dual stain performed on the cervical specimen to predict high-grade disease, determined by LBC, was superior to that of the dual stain performed on the vaginal specimen: 100% (CI 84.6-100%) versus 68.2% (CI 45.1-86.1%). CONCLUSION: Although further evaluation may be warranted, these findings indicate that dual-stain testing of vaginal specimens cannot be advocated as part of cervical screening programmes in low- and middle-income countries. However, dual-stain cytology performed on cervical specimens may have a role in quality assurance in such settings.

Women's knowledge of maternal danger signs during pregnancy: Findings from a cross-sectional survey in Papua New Guinea.

OBJECTIVE: To explore knowledge of pregnancy related danger signs among women attending antenatal clinics in Papua New Guinea. DESIGN: Cross-sectional survey undertaken as part of a wider integrated health and demographic survey. SETTING: Three sites in Papua New Guinea: Hiri District (Central Province), Karkar (Madang Province) and Asaro (Eastern Highlands Province). PARTICIPANTS: 482 women aged 15-44 years. FINDINGS: Almost all (95.2%; 459/482) women attended for antenatal care at least once; 68.2% attended four or more times. Among women who attended the antenatal clinic, 53.6% (246/459) reported receiving information about danger signs in pregnancy from a health worker. Of these 60.2% (148/246) could recall at least one danger sign. In addition, 16.4% (35/213) of women who did not receive information from the antenatal clinic reported pregnancy related danger signs. Among the 183 women who reported danger signs, 47.5% (87/183) reported fever; 39.3% (72/183) reported vaginal bleeding and 36.6% (67/183) reported swelling of the face, legs and arms. Women who reported receiving information at the antenatal clinic were significantly more likely know any danger signs, compared with women who did not receive information at the antenatal clinic (OR 7.68 (95%CI: 4.93, 11.96); p = <0.001). Knowledge of danger signs was significantly associated with secondary school education, compared with none or only primary education (OR 3.08 (95% CI: 2.06, 4.61); p = <0.001). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Every antenatal clinic visit should be used opportunistically to provide women with information about key danger signs during pregnancy and childbirth. Recognising maternal danger signs, together with the importance of seeking early transfer to the health facility and the importance of attending for a health facility birth are critical to improving outcomes for mothers and babies especially in low income settings such as Papua New Guinea.

A diagnostic evaluation of a molecular assay used for testing and treating anorectal chlamydia and gonorrhoea infections at the point-of-care in Papua New Guinea.

OBJECTIVES: Papua New Guinea has among the highest prevalences of sexually transmissible infections (STIs) globally with no services able to accurately test for anorectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections. Here we prospectively evaluated the diagnostic performance of a molecular CT/NG assay used at the point-of-care (POC) with the aim of enhancing anorectal STI screening and same-day treatment. METHODS: Men who have sex with men, transgender women and female sex workers taking part in Papua New Guinea's first large-scale biobehavioural study were enrolled and asked to provide a self-collected anorectal swab for POC GeneXpert CT/NG testing. Same-day treatment was offered if positive. A convenience sample of 396 unique and randomly selected samples were transported to Australia for comparison using the Cobas 4800 CT/NG test (Roche Molecular Diagnostics, Pleasanton, CA, USA). RESULTS: A total of 326 samples provided valid results by Cobas whereas 70 samples provided invalid results suggesting inhibition. The positive, negative and overall percentage agreements of GeneXpert CT/NG for the detection of C. trachomatis were 96.7% (95% CI 92.3%-98.9%), 95.5% (95% CI 91.3%-98.0%) and 96.0% (95% CI 93.3%-97.8%), and for N. gonorrhoeae were 93.0% (95% CI 86.1%-97.1%), 100.0% (95% CI 98.3%-100.0%) and 97.8% (95% CI 95.6%-99.1%), respectively. CONCLUSIONS: The overall rate of agreement between the GeneXpert and Cobas CT/NG assays was high with 96.0% for C. trachomatis and 97.8% for N. gonorrhoeae. Results from this study data suggest that the GeneXpert CT/NG assay is suitable for testing self-collected anorectal specimens at the POC and that same-day treatment was feasible.

Evaluation of self-collected vaginal specimens for the detection of high-risk human papillomavirus infection and the prediction of high-grade cervical intraepithelial lesions in a high-burden, low-resource setting.

OBJECTIVES: To compare the performance of self-collected vaginal (V) specimens with clinician-collected cervical (C) specimens for detection of high-risk human papillomavirus (hrHPV) and cervical disease using the Cepheid Xpert HPV, Roche Cobas 4800 HPV and Hologic Aptima HPV assays. METHODS: Women aged 30-59 years (n = 1005) were recruited at two clinics in Papua New Guinea, and they provided specimens for testing at point-of-care using the Xpert HPV Test, and for subsequent testing using the Cobas HPV (n = 981) and Aptima HPV (n = 983) assays. Liquid-based cytology was performed on C specimens to predict underlying high-grade squamous intraepithelial lesions (HSIL). V specimen results of each assay were evaluated against a constructed reference standard and for detection of HSIL or worse. RESULTS: There was substantial (κ >0.6) agreement in hrHPV detection between V and C specimens across all three assays. The sensitivity, specificity, and positive and negative predictive values of Xpert HPV using self-collected V specimens for the detection of HPV type 16 according to the constructed reference standard were 92.1%, 93.1%, 63.6% and 98.9%, respectively; compared with 90.4%, 94.3%, 67.8% and 98.7% for Cobas 4800 HPV; and 63.2%, 97.2%, 75.0% and 95.3% for Aptima HPV. Similar results were observed for all hrHPV types (combined) and for HPV types 18/45, on all three assays. The detection of any hrHPV using self-collected specimens had high sensitivity (86%-92%), specificity (87%-94%) and negative predictive value (>98%) on all assays for HSIL positivity. CONCLUSIONS: Xpert HPV, using self-collected vaginal specimens, has sufficient accuracy for use in point-of-care 'test-and-treat' cervical screening strategies in high-burden, low-resource settings.

Innovative approaches to cervical cancer screening in low- and middle-income countries.

The estimated cervical cancer burden is over ten-fold greater in low- and middle-income countries (LMICs) than in high-income countries. This health gap is thought to be primarily due to limited access to effective screening and treatment programs for cervical pre-cancer and cancer in such settings. The World Health Organization advocates a policy of 'screen and treat' approach to cervical screening in LMICs and subsequently visual inspection of the cervix with acetic acid (VIA) or Lugo's iodine (VILI), followed by ablative cervical cryotherapy if indicated, and this policy has been implemented in many high-burden settings. The performance of VIA/VILI as a primary screening tool for the detection of cervical pre-cancer and cancer has, however, been inconsistent. Recently, many high-income countries have integrated HPV-DNA testing into their cervical cancer screening programs. The comparatively high cost and resource requirements of HPV-based screening have to date prevented many LMICs from doing the same. A significant development has been the entrance of innovative, easy-to-use and highly accurate HPV tests that can be provided at point of care; these could enable LMICs to implement 'test and treat' approaches for cervical cancer screening.

Ambiguous bodies, uncertain diseases: knowledge of cervical cancer in Papua New Guinea.

OBJECTIVES: Within their local realities, people experience and interpret disease in diverse ways that do not necessarily correlate or converge with Western biomedical interventions. In the high cervical cancer burden setting of Papua New Guinea, understanding how people experience and interpret cervical cancer is necessary for effective intervention. Drawing on work by Street on the production of unstable biomedical knowledge, we explored how ambiguity and uncertainty, coupled with cultural taboos and linguistic limitations, affect what and how people 'know' about women's reproductive organs and their associated disease. DESIGN: A qualitative research approach was used to explore and understand how people in PNG articulate matters of health and disease as they relate to cervical cancer and HPV infection. Specifically, how unstable biomedical knowledge is produced and sustained. We employed a mixed-methods approach in collecting data from 208 (147 women) participants between 2011 and 2012 across 3 provinces in PNG. RESULTS: We found that knowledge and awareness about cervical cancer were poor. Five thematic areas emerged in our analysis, which included the gendered knowledge of women's reproductive health, the burden of cervical cancer in the community and the role (or limitation) of language. We further identified four ways in which ambiguity and uncertainty operate on both sociocultural and biological levels, and in the intersection between to produce unstable biomedical knowledge. These included poor knowledge of where the cervix is located and the uncertainty or unreliability of (lay) diagnoses of disease. CONCLUSION: Local understandings of cervical cancer reflected the limitations of Tok Pisin as a lingua franca as well as the wider uncertain biomedical environment where diagnoses are assembled and shared. There is a clear need to improve understanding of the female reproductive organs in order that people, women in particular, can be better informed about cervical cancer and ultimately better receptive to intervention strategies.

Field Evaluation of Xpert HPV Point-of-Care Test for Detection of Human Papillomavirus Infection by Use of Self-Collected Vaginal and Clinician-Collected Cervical Specimens.

The World Health Organization has recommended that testing for high-risk human papillomavirus (HPV) (hrHPV) infection be incorporated into cervical screening programs in all settings worldwide. In many high-burden, low-income countries, it will not be feasible to achieve high cervical screening coverage using hrHPV assays that require clinician-collected samples. We conducted the first evaluation of self-collected vaginal specimens compared with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. Women aged 30 to 54 years attending two well-woman clinics in Papua New Guinea were invited to participate and provided self-collected vaginal and clinician-collected cervical cytobrush specimens. Both specimen types were tested at the point of care by using the Xpert HPV test. Women were given their cervical test result the same day. Those with a positive hrHPV test and positive examination upon visual inspection of the cervix with acetic acid were offered same-day cervical cryotherapy. A total of 1,005 women were enrolled, with 124 (12.3%; 95% confidence interval [CI], 10.3%, 14.4%) being positive for any hrHPV infection. There was a 99.4% overall percent agreement (OPA) between vaginal and cervical tests for HPV-16 (95% CI, 98.9%, 99.9%), a 98.5% OPA for HPV-18/45 (95% CI, 97.7%, 99.3%), a 94.4% OPA for other hrHPV infections (95% CI, 92.9%, 95.9%), and a 93.4% OPA for all hrHPV types combined (95% CI, 91.8%, 95.0%). Self-collected vaginal specimens had excellent agreement with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. This approach provides for the first time an opportunity to incorporate point-of-care hrHPV testing into clinical cervical screening algorithms in high-burden, low-income settings.