Field trial of a novel point-of-care HPV ‘self-collect, test and treat’ cervical screening strategy for women in low- and middle-income countries: the HPV-STAT study, Papua New Guinea

ISRCTN	ISRCTN13476702
DOI	https://doi.org/10.1186/ISRCTN13476702
Protocol serial number	Nil known
Sponsor	Kirby Institute UNSW Sydney
Funder	National Health and Medical Research Council

Submission date: 11/09/2018
Registration date: 25/09/2018
Last edited: 26/07/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Cancer of the cervix is the most common cancer in women in many developing countries, including Papua New Guinea. If detected early enough, cervical cancer can be cured. Unfortunately, the majority of women in many developing countries do not know they have cervical cancer until it is too late, when the disease cannot be cured. In Papua New Guinea, screening for cervical cancer using Pap smear testing has proved difficult especially in rural areas, because women find it too hard to return to the clinic for their test results. Screening efforts based on an internal examination and the application of dilute vinegar to the cervix to identify early stage disease (known as VIA) have also been disappointing.
Recent studies in countries across the world have shown that screening women for the virus that causes cervical cancer (the human papillomavirus or HPV) can help detect cancer at an early stage and save lives. This study will look at a new way to screen for cervical cancer. In this study, women in Papua New Guinea will be tested for HPV infection when they come to clinic. Women will be given their test results the same day. Women having a positive HPV test will have an internal examination and offered same-day curative treatment.

Who can participate?
Adult women aged 30-59 years who attend Well Woman Clinics in Alotau, Kokopo, Madang, and Mt Hagen, Papua New Guinea.

What does the study involve?
A total of around 4000 women will be asked to take part in the study. Women will be asked some questions about their general health and their sexual and reproductive health. Participants will also be asked to provide a self-collected vaginal specimen for HPV testing that will be conducted in the clinic on the same day. Each HPV test will take around 60 minutes to complete. HPV test results will be provided to women on the same day.
Women who have a positive HPV test will be asked to undergo an internal examination and will be offered curative treatment. During the examination, an additional specimen for laboratory testing will be collected from the cervix. This specimen will be sent to Australia where it will be looked at in a specialist laboratory to see if there is cervical pre-cancer or cancer present. The cervix will be treated using either a freezing device (cryotherapy) or a heating device (thermocoagulation). Women will be asked to come back to the clinic for review in 3 months and 12 months’ time. At the 3 month review, women will be given the results of laboratory tests carried out in Australia.
Women who have a negative HPV test will be advised that no further examination or treatment is required but that they should return for repeat screening in 3 years’ time. Some HPV negative women (around 15%) will be asked to provide additional specimens for laboratory testing in Australia, as described above. This will allow the study team to compare test results between HPV positive and negative women. These women will also be asked to come back to the clinic in 3 months’ time when they will be given the results of the additional laboratory tests carried out in Australia.
Finally, some women may be asked to take part in an additional interview or a small group discussion. These will help us understand what women think about the care they received, and the costs involved in coming to the clinic for screening.

What are the possible benefits and risks of participating?
The study will provide valuable information for researchers, health staff and policy makers seeking to improve the sexual health of women, families and communities in PNG. Women who participate in the study may benefit directly from taking part as a result of receiving an HPV test and any treatment that they receive.
There are no risks involved in collecting genital swabs and testing them for HPV infection.
Women who undergo cervical treatment may experience mild-to-moderate discomfort when the treatment is being given in the clinic. They may also experience a small amount of vaginal discharge, or might notice some small spots of blood in their underwear (‘spotting’) for up to one-week following the procedure. Women who receive treatment will be advised to abstain from sexual intercourse until all discharge has ceased. Some women may feel slightly uncomfortable or embarrassed when asked questions about their sexual health. All study interviewers are trained staff with experience in asking such questions and will do their best to avoid any such feelings arising during the study.

Where is the study run from?
Papua New Guinea Institute of Medical Research (PNGIMR) (Papua New Guinea)

When is the study starting and how long is it expected to run for?
July 2017 to March 2021

Who is funding the study?
National Health and Medical Research Council (NHMRC) (Australia)

Who is the main contact?
Dr Andrew Vallely
avallely@kirby.unsw.edu.au

Contact information

Dr Andrew Vallely
Scientific

The Kirby Institute, UNSW Sydney
Wallace Wurth Building
Sydney
2052
Australia

Phone	+61 420 822 319
Email	avallely@kirby.unsw.edu.au

Study information

Primary study design	Observational
Study design	Observational prospective multi-centre longitudinal cohort study
Secondary study design	Longitudinal study
Study type	Participant information sheet
Scientific title	Prospective cohort study to evaluate point-of-care HPV-DNA testing for the early detection and treatment of cervical pre-cancer in high-burden, low-resource settings
Study acronym	HPV-STAT
Study objectives	Point-of-care HPV-DNA testing is effective, cost-effective, acceptable to women and health providers and can be scaled up within existing health systems for primary cervical screening in low- and middle-income countries.
Ethics approval(s)	1. Papua New Guinea Institute of Medical Research (PNGIMR) Institutional Review Board (IRB), 12/04/2018, IRB No. 1712 2. Papua New Guinea National Department of Health Medical (NDoH) Research Advisory Committee (MRAC), 05/06/2018, MRAC No. 17.36 3. University of New South Wales (UNSW) Human Research Ethics Committee (HREC), 21/02/2018, HREC No. HC17631
Health condition(s) or problem(s) studied	Cervical pre-cancer and cervical cancer
Intervention	Point-of-care HPV-DNA testing using self-collected vaginal specimens tested on the Cepheid GeneXpert platform (Xpert HPV Test). Women having a positive HPV test result are offered a pelvic examination and same-day cervical ablation using cryotherapy or thermocoagulation. Visualisation of the cervical transformation zone prior to ablation is aided by the application of dilute vinegar (acetic acid) as per current international and national guidelines for the conduct of visual inspection with acetic acid (VIA). At enrolment, women will be offered same day HPV-DNA testing, and treatment if HPV positive. Women who are HPV positive plus a 15% randomly selected sub-population of HPV negative women will be asked to provide additional cervical specimens for off-site liquid based cytology (to be conducted in Melbourne), and to re-attend in three-months. Women who were HPV positive at enrolment, plus a 15% randomly selected sub-population of women who were HPV negative at enrolment, will be asked to re-attend to receive baseline cytology results. Women who were HPV positive at enrolment will be asked to re-attend for repeat HPV-DNA testing and clinical review as indicated. Some women may be asked to take part in an additional interview or a small group discussion. These will help us understand what women think about the care they received, and the costs involved in coming to the clinic for screening.
Intervention type	Other
Primary outcome measure(s)	The performance of the Xpert HPV Test for the detection of underlying high-grade intraepithelial lesions (HSIL) when provided at point-of-care using self-collected vaginal specimens. Performance for the detection of underlying HSIL will be evaluated using the following standard diagnostic evaluation criteria: 1. Sensitivity 2. Specificity 3. Positive predictive value 4. Negative predictive value We will calculate the sensitivity, specificity, positive and negative predictive values (with 95% confidence intervals) of the Xpert HPV Test to detect HSIL. Performance will be evaluated at enrolment.
Key secondary outcome measure(s)	The following will be assessed at the baseline, around 3-6 months after enrolment (study mid-point) and 12-18 months after enrolment (end of the trial): 1. Cost-effectiveness of point-of-care Xpert HPV testing for the early detection and treatment of cervical pre-cancer lesions. Standard cost-effectiveness analyses will be performed by identifying the cost-effectiveness frontier and calculating the incremental cost-effectiveness ratios (ICERs) of strategies on the frontier compared to the next most cost-effective strategy. We will calculate all cost-effectiveness ratios as cost per life year saved. 2. Health system implementation requirements of point-of-care Xpert HPV testing for the early detection and treatment of cervical pre-cancer lesions. Health system implementation challenges and benefits will be evaluated in terms of: 2.1. Patient-flow and turnaround-time 2.2. Work-flow and staff time 2.3. Training and supervision needs 2.4. Procedures for finance, payment and health information 2.5. Logistics and management 2.6. Shifts in client-provider relationships when moving from current routine screening (based on VIA alone or Pap test) to HPV-based screening. 3. Acceptability of point-of-care Xpert HPV testing for the early detection and treatment of cervical pre-cancer lesions: 3.1. Acceptability of the intervention from client and health provider perspectives will be analysed using quantitative and qualitative methods 3.2. Key findings from each approach will be triangulated in order to allow robust conclusions to be made regarding acceptability. 3.3. We will calculate the proportion of women who consider the intervention ‘acceptable’ or ‘highly acceptable’ using quantitative data collected in study-specific CRFs 3.4. Qualitative data will be collected from study participants, clinic staff, health managers and other key stakeholders in the pre-intervention and intervention phases of the study in focus group discussions (FGDs) and semi-structured interviews (SSIs) that will investigate women’s preferences for service delivery and the wider societal and cultural contexts within which the acceptability of new interventions for cervical cancer are framed and perceived. 4. Laboratory performance of self-collected vaginal specimens compared with clinician-collected cervical specimens for the detection of cervical cancer biomarkers. Laboratory performance characteristics (sensitivity, specificity, positive and negative predictive value) of self-collected compared with clinician-collected specimens for the detection of cervical cancer biomarkers will be calculated as proportions with 95% confidence intervals.
Completion date	30/03/2021

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Sex	Female
Target sample size at registration	4000
Total final enrolment	4285
Key inclusion criteria	1. Aged 30-59 years 2. Attending a participating Well Woman Clinic 3. Willing to provide self-collected vaginal swabs for baseline Xpert HPV testing 4. Willing to comply with study follow-up procedures 5. Willing to undergo a clinical interview and pelvic examination 6. Willing to provide self-collected and clinician-collected specimens for laboratory investigations 7. Able to complete study informed consent procedures, to understand why the study is being carried out, and the potential risks and benefits associated with study participation; 8. Able to provide reliable contact details to facilitate future community tracing and follow-up
Key exclusion criteria	1. Currently pregnant or given birth in the last 6 weeks 2. Previous diagnosis of cervical cancer and/or has had a hysterectomy 3. Permanent disability, that prevents or impedes study participation and/or comprehension (such that it is not possible to obtain informed consent to participate) 4. Women having their menstrual period at the time of the clinic visit will be advised to return for screening in 1-2 weeks
Date of first enrolment	06/06/2018
Date of final enrolment	30/12/2020

Locations

Countries of recruitment

Australia
Papua New Guinea

Study participating centre

Papua New Guinea Institute of Medical Research

Homate Street
Goroka
EHP 441
Australia

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		22/07/2022	26/07/2022	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Protocol file	version 0.4	30/09/2019	18/08/2021	No	No

Additional files

ISRCTN13476702_Protocol_v0.4_30Sep2019.pdf: Protocol file

Editorial Notes

26/07/2022: Publication reference added.
18/08/2021: The following changes have been made:
1. The uploaded protocol file has been updated.
2. The public title has been changed from "HPV Point of Care Study: Field evaluation of a novel ‘test and treat’ cervical cancer screening strategy for women in low- and middle-income countries" to "Field trial of a novel point-of-care HPV ‘self-collect, test and treat’ cervical screening strategy for women in low- and middle-income countries: the HPV-STAT study, Papua New Guinea".
3. The study acronym has been changed from "HPV POC Study PNG" to "HPV-STAT".
4. The plain English summary has been updated to reflect the increased number of participants.
05/08/2021: The following changes have been made:
1. Protocol file uploaded.
2. The final enrolment number has been added
02/08/2021: The total target enrolment has been changed from 3400 to 4000.
04/07/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/06/2019 to 30/12/2020.
2. The overall trial end date was changed from 31/12/2020 to 30/03/2021.
3. The intention to publish date was changed from 01/03/2021 to 30/09/2021.