Evaluation of Human Papilloma Virus (HPV) Self-testing to Increase Screening Uptake

Related Clinical Trial
Conservative Management of HSIL in Patients With Future Pregnancy Aspiration Clinical Validation of Cervical Cancer Screening Methods Comparison of LLETZ Versus LEEP for the Treatment of Cervical Dysplasia Effectiveness of Cervical Screening in Unvaccinated, Herd Effect Protected Women (HPV400) Virtual Reality: Influence on Satisfaction, Pain, and Anxiety in Patients Undergoing Colposcopy Treatment of Cervical Intraepithelial Neoplasia (CIN) Grade III With Non-invasive Physical Plasma Immuno-persistence Study of a Recombinant Human Papillomavirus 16/18 Bivalent Vaccine in Preadolescent Girls (54m) Pembrolizumab for the Treatment of High-Grade Vulvar, Vaginal, or Cervical Intraepithelial Neoplasia Self-Testing Options in the Era of Primary HPV Screening for Cervical Cancer Trial DNA Methylation Testing for the Screening of Uterine Cervical Lesion Immunohistochemical Staining of p16 for the Screening of Cervical Cancer CASUS: Validation for Detection of Precursor Lesions CASUS: Improved and Quality Assured Collection of First-void Urine Efficacy and Safety of Cevira® in Patients With Cervical Histologic High-grade Squamous Intraepithelial Lesions (HSIL) Lugol’s Solution in Addition to Acetic Acid During Colposcopy A Phase I Study of E7 TCR T Cell Immunotherapy for High-Grade Cervical Intraepithelial Neoplasia Imiquimod, Fluorouracil, or Observation in Treating HIV-Positive Patients With High-Grade Anal Squamous Skin Lesions Primary Imiquimod Treatment Versus Surgery for Vulvar Intraepithelial Neoplasia Safety and Effectiveness of Giving Isotretinoin to HIV-Infected Women to Treat Cervical Tumors Costa Rican Natural History Study of HPV and Cervical Neoplasia Measurement of Digital Colposcopy for Fluorescence Spectroscopy of TNC Using a Second Device Effect of Salpingectomy During Conservative Hysterectomy Feasibility of Delphi Screener for Cervical Cytology Study of Topical ABI-1968 in Subjects With Precancerous Cervical Lesions From Human Papillomavirus (HPV) Infection. Study of Topical ABI-1968 in Subjects With Precancerous Cervical Lesions From Human Papillomavirus (HPV) Infection Gene Therapy Follow up for Subjects Previously Enrolled in NCI Experimental Transplantation and Immunology Branch Studies Home-Based or Clinic-Based Human Papillomavirus (HPV) Screening Viral Load Determination and Biomarkers of High Risk Human Papillomavirus (HPV) – Types in HIV-positive Men Immuno-persistence Study of a Recombinant Human Papillomavirus 16/18 Bivalent Vaccine in Preadolescent Girls A Bridging Study of a Recombinant Human Papillomavirus 16/18 Bivalent Vaccine in Preadolescent Girls TWO DİFFERENT ELECTROSURGERY DEVICES AS MONOPOLAR HOOC AND PLASMAKINETIC BIPOLAR SPATULA EFFECTIVENESS DURING COLPOTOMY Minimally Invasive Benign Hysterectomy HRME in the Screening of Cervical Cancer Precursor Lesions in Brazil (UH3 – Brazil) Diagnostic Imaging Aid for Management of Cervical Lesions Cervical Cancer Early Endpoints and Determinants Triage Strategies in Cervical Cancer Prevention Genotypification and Predisposing Factors in Human Papilloma Virus Infection Development of Immunological Assays for the Evaluation of Tumor Antigen Specific Immunity Chinese Cancer Prevention Study(CHICAPS) The Development of a “Mother/Child, Screen, Treat and Vaccinate Program” in Manchay and Iquitos, Peru HRME: Screening for Cervical Cancer and Its Precursors in Low‐Resource Settings A Trial for Patients With Advanced/Recurrent Cervical Cancer HPV Genotyping by DR. HPV Genotyping in Vitro Diagnostic Device (IVD) Kit in Exfoliated Cells of the Uterine Cervix Human Papillomavirus (HPV) and Risk of Cervical Precancer and Cancer Self-sampling for Non-attenders to Cervical Cancer Screening HPVPro Study: Comparison of HPV Detection in Clinician-collected Cervical Swabs and Self-sampled Cervicovaginal Swabs Acceptability and Efficacy of Self-sampling for Cervical Cancer Screening: A Pilot Study Clinical Trial for the Use of a Novel Cell Collector Device to Retrieve Cells From the Uterine Cervix Human Papillomavirus Epidemiology in Nigeria Impact of HPV Vaccine On The Prevalence Of HPV In Norway Deciphering Mechanisms Underlying Cancer Immunogenicity Expression of Oncogenic Human Papillomavirus E6/E7 Protein in Tampon Self-Tests Spectroscopic Evaluation of Cervical Neoplasia Evaluating the 2-dose Immunization Schedule of Human Papillomavirus (HPV)-16/18 in Adolescent Females Immune Response to the Human Papillomavirus Vaccine in Young Women With Inflammatory Bowel Disease Safety and Efficacy Study of Antiviral Local Application to Treat High Grade Cervical Intraepithelial Lesions (CIN2/3) Human Papilloma Virus (HPV) Vaccine Trial in Young Adolescent Women With GlaxoSmithKline Biologicals’ (GSK Bio) HPV-16/18 Vaccine Participation in Screening for Cervical Cancer: Interest of a Self-sampling Device Provided by the General Practitioner Self-sampling and Human Papillomavirus (HPV)-Testing for Unscreened Women in Cervical Cancer Prevention Human Papillomavirus (HPV) Vaccine Consistency and Non-inferiority Trial in Young Adult Women DNA Methylation Biomarkers for Cervical Cancer Screening Evaluation of in Vitro Devices on Self-collected Vaginal Swab and Urine Sample for Testing of Human Papilloma Virus The SAFE Study: Satisfaction and Adherence to Follow-Up With Colposcopy Exams Impact of AV2 Antiviral Drug on the Treatment of HPV-associated Lesions of the Uterine Cervix Can Text Reminders Improve Uptake of Cervical Screening? Comparing Two Techniques of Haemostasis After Cervical Conization A Comparison Study of Two Community Outreach-Based Approaches to Increase Participation of Women Living in the Mississippi Delta in Cervical Cancer Screening FASTER-Tlalpan Study HPV Integration Testing for Human Papillomavirus-Positive Women Randomized Implementation of Primary HPV Testing in the Organized Screening for Cervical Cancer in Stockholm Dose-Ranging Study of Recombinant Human Papillomavirus Virus 16/18 Bivalent Vaccine Cervical Cytology – Do SMS Reminders Increase Participation in the Cervical Screening Programme? Comparison of Pelvic Lymphadenectomy Versus Isolated Sentinel Lymph Node Biopsy Procedure for Early Stages of Cervical Cancers : a Multicenter Study With Evaluation of Medico-economic Impacts The Study of Folate Receptor-Mediated Staining Solution (FRD™) In Cervical Lesion Detection Effectiveness of Cervical Screening in HPV Vaccinated Women Randomized Controlled Trial to Study Interventions to Increase Participation in Cervical Cancer Screening Program Human Papillomavirus (HPV) Testing to Improve Cervical Cancer Screening in the Mississippi Delta Validation of Human Papillomavirus Assays and Collection Devices for Self-samples and Urine Samples Effect of Fee on Attendance in Cervical Cancer Screening Cervix Cytological Screening – Comparison of Tampon Self-Test and the Routine Smear. Study of the Diagnostic Efficacy of “Real Time” Niris 1300e Optical Coherence Tomography (OCT) Imaging System in the Management of Pre-invasive and Invasive Neoplasia of the Uterine Cervix LLETZ Under General Versus Local Anesthesia Buffered Lidocaine for Loop Electrosurgical Excision Procedures (LEEPs) Trial on Safety and Pharmacokinetics of Intravaginal Curcumin IMproved PRactice Outcomes and Value Excellence in Colposcopy Visual Inspection With Acetic Acid Compared to Lugol’s Iodine in HIV-infected Women Phase I, Open-Label Study of the Safety, Tolerability, and Immunogenicity PEK Fusion Protein Vaccine Clinical Evaluation of Polarized Light Assisted Colposcopy Indirect Comparison Topotecan Cervical Carcinoma Meta-analysis of Efficacy of Topotecan Efficacy Study of Diathermy Cone Biopsy for the Treatment of Cervical Intraepithelial Lesion Quality of Life in Thai Women Diagnosed Cervical Cancer at King Chulalongkorn Memorial Hospital Serum IGF-II and Cancer: Can IGF II Levels be Used to Monitor and Screen Patients Specifically for Cervical Cancer A Follow-up Extension Study to Evaluate the Persistence of Immune Response to GSK Biologicals’ HPV Vaccine in Healthy Chinese Female Subjects Who Received Three Doses of the Vaccine in the HPV-058 Study TMTP1-ICG Mapping in Colposcopy-directed Biopsy Hemodynamic Stability of Bupivacaine With and Without Adrenaline for Paracervical Block for Cervical Conization Immediate Treatment vs Colposcopic Follow-up for Biopsy-Proven CIN 1 Diagnosis of Cervical Lesions in Women With Unhealthy Looking Cervix Construct Validity of a Large Loop Excision of the Transformation Zone (LLETZ) Training Model Endocervical Evaluation With the Curette Versus Cytobrush for the Diagnosis of Dysplasia of the Uterine Cervix Randomized Controlled Trial of Human Papillomavirus Testing in Primary Cervical Cancer Screening Safety and Efficacy of GX-188E DNA Therapeutic Vaccine Administered by Electroporation After Observation The HPV Self-test as a Test of Cure in Madagascar REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL) A Trial of Two Electrosurgical Conizations: Histopathological Analysis of Excision Margins Cold Knife Conization With and Without Lateral Hemostatic Sutures DC Vaccines Targeting HPV16/18 E6/E7 Protein to Regress CINI/CIN2 A Phase III Study of Human Papillomavirus (HPV)-16/18 Vaccine. Evaluation of Human Papilloma Virus (HPV) Self-testing to Increase Screening Uptake Improving Cervical Cancer Screening Among HIV-Infected Women in India REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL) Compass – Randomised Controlled Trial of Primary HPV Testing for Cervical Screening in Australia chemQbiosciences:Manual Liquid Based Cytology A Dose-finding Study of MAL and HAL Photodynamic Therapy of Cervical Premalignant Lesions. Diagnostic and Prognostic Value of p16INK4a Expression in Low Grade Squamous Intraepithelial Lesions of the Cervix. Music Listening to Reduce Pain and Anxiety During LEEP A Comparison of Immediate Treatment of CIN1 With Cryotherapy and 12 Month Cytology Follow up in HIV Seropositive Women Aminolaevulinic Acid Photodynamic Therapy of Cervical Persistent HPV Infection and Cervical Neoplasia HPV DNA Vaccine Via Electroporation for HPV16 Positive Cervical Neoplasia The Correlations Between HPV L1-Specific Immunologic Responses in Cervical Cancer and Cervical Intraepithelial Neoplasia (CIN) Patients and Their Prognosis Safety and Tolerability of Cidofovir Gel Applied on Cervix Squamous Lesions Lidocaine Spray Compared With Submucosal Injection During LEEP: a Randomized Controlled Trial A Post Marketing Surveillance (PMS) Study to Monitor the Safety of GlaxoSmithKline (GSK) Biologicals’ Human Papillomavirus (HPV) Vaccine in Female Chinese Subjects Comparison of Human Papillomavirus Integrated DNA and Messenger RNA in Cervical Neoplasia Cervical And Self-Sample In Screening Study Randomized Trial of Vaginal Self Sampling for Human Papillomavirus (HPV) Factors Associated With Residual Disease In The Central Cone Trial to Evaluate Single- and Double- Freeze Cryotherapy in the Prevention of Cervical Neoplasia Colposcopy Versus HPV Testing to Identify Persistent Cervical Precancers Optimal Strategy for the Management of ASCUS Cytology in Health Care Services of Medellin, Colombia V501 Safety and Efficacy Study in Japanese Women Aged 16 to 26 Years (V501-110) Effectiveness of HPV Vaccine in Thai Adult Women Topical Fluorouracil and Imiquimod in Treating Patients With High-Grade Cervical Intraepithelial Neoplasia Dose-finding Study of Hexaminolevulinate (HAL) Photodynamic Therapy (PDT) to Treat Cervical Neoplasia Artesunate Vaginal Inserts for the Treatment of CIN2/3 A Two-Stage Phase 2 Study Of A-007 Topical Gel in High-Grade Squamous Intraepithelial Lesions (HSIL) Trial23 – A Method Study on Cervical Screening in Women Offered HPV-vaccination as Girls An Innovative Treatment for Cervical Pre Cancer A Study of Amolimogene (ZYC101a) in Patients With High Grade Cervical Intraepithelial Lesions of the Uterine Cervix LLETZ Under Direct Colposcopic Vision The Efficacy of Tachosil® for Prevention of Hemorrhage After Loop Electrosurgical Excisional Procedure (LEEP) Safety and Efficacy of GX-188E DNA Therapeutic Vaccine Administered by Electroporation After Observation LLETZ With Videocolposcopy Versus LLETZ With Binocular Colposcopy Imiquimod Treatment of Residual or Recurrent CIN Lesions: a Study Protocol Colposcopy and Dynamic Spectral Imaging (DSI) Imiquimod Treatment of High-grade CIN Treatment of High-Grade Pre-Neoplastic Cervical Lesions (CIN 2/3) Safety and Efficacy of GX-188E Administered Via EP Plus GX-I7 or Imiquimod. Topical Imiquimod vs. LEEP for Women With Carcinoma In-situ of the Cervix Feasibility of the Management of Severe Cervical Dysplasia in a Single Visit Video Colposcopy in Women With Dysplasia Randomized Clinical Trial on Clinical Management of ASCUS and LSIL (ALTS) Imiquimod Treatment of CIN Lesions HPV Integration Testing for Cervical Cancer Screening Hemostatic Procedure After Biopsy of the Cervix HPV-cytology Testing Versus Cytology Testing for the Detection of High Grade CIN An Exploratory Safety and Immunogenicity Study of HPV16+ Immunotherapy VB10.16 in Women With HSIL; CIN 2/3) Safety and Efficacy of A-007 Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix Prevaccination Study of Cervical Human Papillomavirus Types in Yangtze River Delta Area, China Green Tea Extract in Preventing Cervical Cancer in Patients With Human Papillomavirus and Low-Grade Cervical Intraepithelial Neoplasia An Assessment of an Attenuated Live Listeria Vaccine in CIN 2+ Phase 2 Clinical Trial to Evaluate the Safety and Efficacy of Plasmid DNA Therapeutic Vaccine(GX-188E) Multispectral Digital Colposcope With Probe for Detection of Cervical Intraepithelial Neoplasia A Study of VGX-3100 DNA Vaccine With Electroporation in Patients With Cervical Intraepithelial Neoplasia Grade 2/3 or 3 Fischer Cone Biopsy Excisor Versus Loop Excision Procedure for Conization A Phase III Randomized Trial of Topical Vaginal Fluorouracil (5-Fluorouracil, 5-FU) Maintenance Therapy Versus Observation After Standard Treatment for High-Grade Cervical Dysplasia in HIV-Infected Women Therapeutic Vaccination for Patients With HPV16+ Cervical Intraepithelial Neoplasia (CIN2/3) Coherence Imaging of the Cervical Epithelium With Scanning a/LCI Vaccine Therapy in Preventing Cervical Cancer in Patients With Cervical Intraepithelial Neoplasia See and Treat in an Outpatient Setting in Women Above 45 Years With Cervical Dysplasia Factors Predicting Persistence of Oncogenic HPV and Cervical Dysplasia in HIV Infected Kenyan Women Smoking Cessation in Women With Gynecological Conditions Recurrence in High-grade Lesions After Conization Evaluation of Initial High Risk Human Papillomavirus (HR-HPV) Viral Load as Predictive Marker for Cervical Intraepithelial Neoplasia Grade 1 (CIN1) Persistence Management of Cervical Intraepithelial Neoplasia Grade 2 Photodynamic Therapy Using Lutetium Texaphyrin in Treating Patients With Cervical Intraepithelial Neoplasia Celecoxib in Treating Patients With Cervical Intraepithelial Neoplasia Aminolaevulinic Acid Photodynamic Therapy for HPV+ Low Grade Cervical Intraepithelial Neoplasia (LSIL;CIN1) An Innovative Treatment for Cervical Precancer (UH3) Evaluating Materials to Educate Patients About Cervical Dysplasia A Efficacy and Safety Study of Composite Gel Containing Black Raspberry Extract in Removing HPV From Patients With Cervical Intraepithelial Neoplasia(CIN) After Cervical Conization Performance, Safety, and Efficacy of a New Cyrotherapy Device for Cervical Dysplasia Performance, Safety, and Efficacy of a New Cryotherapy Device for Cervical Dysplasia [Part II] Music and Colposcopy in Women With Cervical Dysplasia. Use of Human Papillomavirus Persistence for Determination of Treatment Efficacy Among Women With Cervical Dysplasia ITIC (Imiquimod Therapy in Cervical Intraepithelial Neoplasia)-Trial A Study of RO5217790 in Participants With High Grade Cervical Intraepithelial Neoplasia (CIN) Associated With High Risk Human Papillomavirus (HR-HPV) Infection Local Hyperthermia for the Treatment of Cervical Intraepithelial Neoplasias Comparison of Cervical CIN II/III Treatment Outcomes With Thermal Ablation Device A Trial to Evaluate the Efficacy and Safety of BLS-ILB-E710c in Patients With Cervical Intraepithelial Neoplasia 2/3 (CIN2/3) A Pilot Study of EM-1421 for the Treatment of Cervical Intraepithelial Neoplasia Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia Dose-finding, Safety Study of Plasmid DNA Therapeutic Vaccine to Treat Cervical Intraepithelial Neoplasia Safety of GX-188E DNA Therapeutic Vaccine Administered by Electroporation to Cervical Intraepithelial Neoplasia Grade 3 Effect of Curcumin in Treatment of Squamous Cervical Intraepithelial Neoplasias (CINs) Study of SOR007 Ointment for Cervical Intraepithelial Neoplasia (CIN) Impact on Disease Relapse of HPV Vaccination in Women Treated With LEEP for Cervical Intraepithelial Neoplasia. HOPE9 Focal Ablation of Cervical Precancer Digital Imaging Aid for Assessment of Cervical Dysplasia Intravaginal Artesunate for the Treatment of HPV+ High Grade Cervical Intraepithelial Neoplasia (CIN2/3) TRICIN: Prospective Study on the Efficacy of Single Topical Trichloroacetic Acid (TCA) 85% in the Treatment of Cervical Intraepithelial Neoplasia (CIN 1/2) Hexaminolevulinate (HAL) Photodynamic Therapy (PDT) of Cervical Intraepithelial Neoplasia (CIN) Grade 1 Validation of Implementation of Cervical Dysplasia Treatment Modalities in HIV-Seropositive Women Vaginal Progesterone in the Treatment of Cervical Dysplasia Grade I and II Testing Use of Condoms on Regression of Cervical Intraepithelial Neoplasia Safety Study to Test the Safety of HspE7 and Poly-ICLC Given in Patients With Cervical Intraepithelial Neoplasia Can Alternative Treatment Have an Impact on Cervical Dysplasia? Forced Versus Spray Coagulation in Women Undergoing LLETZ-conization for Cervical Dysplasia: a Randomized Trial Efficacy and Safety Study of PGA (Poly-gamma Glutamic Acid) for Cervical Intraepithelial Neoplasia Oral Diindolylmethane (DIM) for the Treatment of Cervical Dysplasia A Phase II Single-arm Intervention Trial of Nelfinavir in Patients With Grade 2/3 or 3 Cervical Intraepithelial Neoplasia A Pilot Study to Evaluate Ultrasonic Surgical Aspiration as a Treatment Modality for Cervical Dysplasia Physical Cold Atmospheric Plasma for the Treatment of Cervical Intraepithelial Neoplasia Efficacy and Safety Study of BLS_ILB_E710c for the Fertile Women With Cervical Intraepithelial Neoplasia(CIN3) Cryotherapy vs. LEEP to Treat Cervical Intraepithelial Neoplasia (CIN) 2/3 Among HIV-positive Women An Alternative Treatment for Cervical Intraepithelial Neoplasia Using the Focal Loop Electrosurgical Excision Procedure

Brief Title

Evaluation of Human Papilloma Virus (HPV) Self-testing to Increase Screening Uptake

Official Title

Study of HPV Self Testing Evaluation in the Province of Jujuy, Argentina

Brief Summary

      Cervical cancer is a leading cause of mortality among women in developing countries. A key
      factor has been the failure to achieve good coverage. The development in the last years of
      HPV-DNA based tests has changed the scenario, because it combines a high performance to
      detect disease with a reduction of screening frequency. Through self-testing, HPV testing has
      the potential of reducing social and health service barriers faced by women to access
      screening.

      This study is carried out in Jujuy, one of the Argentinian provinces with highest cervical
      cancer mortality rates and where HPV testing has been introduced as a primary screening test
      for all women attending public health sector. The study was conducted between July
      2012-December 2013, and supported by the Argentinean National Cancer Institute. The protocol
      was approved by the institutional review committees of the Ministry of Health of Jujuy.

      This trial is a randomized by population clusters study that aims to assess the effectiveness
      of self-testing to increase coverage. The aims of this study are: a) to assess the self-test
      effectiveness to increase the participation of women in screening programs, b) to assess the
      self-test acceptability by women, c) to assess HPV self-test effectiveness measurement for
      the detection of CIN2+ lesions against cytology in primary screening.

      An overall number of 200 community health workers (CHWs) from the Primary Health Care System
      (PHCS) of Jujuy will be randomized into two groups that will be named Self-test Group (ST)
      and Conventional Sample Group (CS):

        1. ST Group: CHWs will invite eligible women of their area to choose between doing a
           self-test or having a conventional sample taken by a health professional of the closest
           health care center.

        2. CS Group: CHWs will invite eligible women in their area to have a conventional sample
           taken by a health care professional of the nearest health care center.

      In order to measure the self-test relative sensitivity against cytology to detect CIN2+ in
      primary screening, all the women in the Self-test Group who have decided to do the self-test
      and all the women of 30 years of age and older that were screened with cytology by the
      provincial program for the prevention of cervical cancer in 2011 will be considered.

      A database built specifically for the study will be used; it will hold the list of eligible
      women to participate in the study. The records of women of 30 years of age and older residing
      in the areas included in the study will be imported from the PHCS databases.

      In addition, the data surveyed by the study will be uploaded: randomization Group, presence
      of the woman at home during the CHW's visit, agreement to participate in the study,
      realization of self-test (in the corresponding group), and if appropriate, reasons for not
      doing the self-test. Lastly, the HPV Test realization will be uploaded importing the data on
      SITAM, (link of data done as from the identity card number).

      Data Analysis

      Self-test acceptability: Acceptability is defined as the number of women accepting the
      self-test against the number of women offered the option between the self-test and the
      conventional sample (proportion of women accepting the self-test). The acceptability in this
      population will be estimated as the average of acceptabilities calculated by CHW, as to
      control the impact of the CHWs on acceptability and reach an appropriate variance estimate.
      Besides, the variability introduced by the CHWs on acceptability will be studied and the
      results obtained by male and female CHWs will be compared, as well as those obtained by the
      CHWs in rural and urban areas.

      Self-test effectiveness to enhance participation of women in screening and diagnosis: There
      will be a comparison of the percentage of women that did the HPV test in the Self-test group
      and the Conventional sample group. Three different coverage indicators will be considered for
      every CHW. These will be defined as the number of women screened within the field work
      regarding:

        1. The number of women reached by the CHW who accepted participating in the study.

        2. The number of eligible women for that CHW (regardless of whether the CHW was able to
           contact them or not).

      The effect of the strategy (offering the self-test option against promotion of the
      conventional sample) will be estimated for each one of the coverage measures using a means
      difference test or a non-parametric test for independent samples.

      CIN 2+ detection rate: The effectiveness of the HPV Self-test against screening cytology to
      detect CIN2+ will be estimated as the detection rates difference and as the detection rates
      ratio. In addition, there will be a comparison of the CIN2+ detection rate in the group of
      women who did the self-test against the total number of women in the province of Jujuy that
      were tested for HPV (conventional sample strategy + triage Pap test) until December 2012.
    

Detailed Description

      Description of the problem and study rationale

      High screening coverage of women at higher risk is an essential component within organized
      cervical cancer (CC) prevention programs. Yet, reaching high levels of coverage is a
      challenge, mainly for programs implemented in developing countries that, in most cases, have
      not achieved high coverage levels to effectively have an impact on the incidence and
      mortality of the disease1,2.

      In Argentina, it is estimated that 40% of poor women have never participated in screening
      programs3. It has been shown that it is among those women with low screening frequency that
      cervical cancer is mainly diagnosed4. In our country, the coverage map shows an inverse
      correspondence with the cervical cancer mortality map. Women living in the Northwest and
      Northeast regions, where mortality rates are highest, are the most likely to be screening
      underusers.

      The lack of information about CC prevention, the lack of support networks, shame related to
      sexuality and the body, and fear of cancer are factors that hinder an informed
      decision-making process by women about their own health care. In turn, the autonomy of women
      is often conditioned by the characteristics of the health systems responding to a top-down
      and medicalized system where there is an asymmetry of knowledge and power between health care
      professionals and users.

      Since the discovery of the causal association between oncogenic HPV (Human Papilloma Virus)
      and CC, new screening HPV detection-based tools have been developed. The hybrid capture HPV
      test (HC2) detects the presence of DNA of the 13 high oncogenic risk types in the woman's
      cervix. It's been proved that the HPV test is highly effective for the detection of
      pre-cancerous lesions and reduction of cervical cancer mortality5.

      In the province of Jujuy CC HC2 is available in all public health centers since 2011, with
      the aim of improving the effectiveness in the detection of high-grade lesions and cancer and
      reduce mortality rates.

      One of the challenges for programs introducing HPV testing is to continue improving the
      screening coverage indicators. This new technology has the potential to reduce screening
      access barriers, given the fact that the HPV test allows for self-testing, a practice that
      can be done at home. With the self-test the woman collects herself a vaginal sample with a
      brush used for that purpose.

      Studies carried out in different countries of the world and Latin America have shown that the
      HPV self-test acceptability is high6. The vaginal self-test allows to overcome some of the
      barriers associated with screening such as geographical accessibility and shame of having a
      sample taken by a health professional. That is, the self-test has a big potential to increase
      screening coverage, allowing women enhanced autonomy for their cervical cancer prevention
      care.

      The HC2 HPV test is a molecular biology technology that detects the presence of 13 high
      oncogenic risk DNA types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) in the
      cervix cells. It is an accurate technology, highly reproducible and with an estimated
      sensitivity of more than 90%, much higher than the cytology. Different studies in Latin
      America and the world account for the HPV Test higher sensitivity against
      cytology7,8,9,10,11,12,13,14.

      At the same time, the HC2 HPV test is the only one in the world whose effectiveness to reduce
      cervical cancer incidence and mortality has been scientifically proved. A study conducted in
      India15 concluded that the rates of incidence and mortality were significantly higher within
      the groups screened with cytology or visual inspection with acetic acid (VIA) as compared to
      the group screened with HC2. HC2 test screening was able to reach a reduction of almost 50%
      in the mortality rate.

      As far as the self-test, its higher sensitivity against cytology for the detection of cervix
      cancer precursor lesions (CIN2+) was also observed in various studies11,16.

      The CIN2+ detection rate (histologically confirmed diagnosis) also shows a relative advantage
      of the HPV test over cytology. Different studies have found that detection of CIN2+ is higher
      in the case of the self-test against cytology 17,18. On the other hand, a study carried out
      in Mexico found that the CIN2+ lesions self-test detection rate is 3.4 times higher over that
      of cytology (relative sensitivity)19.

      Setting of the study

      The province of Jujuy was selected to develop this study due to the fact that screening based
      on HPV testing as a primary test was introduced in 2011. The province of Jujuy has a high
      mortality rate (11.8 x 100.000 women over the 2008-2011 period) and it is one of the
      provinces set as a priority in the National Program for the Prevention of Cervical Cancer.
      The Primary Health Care System (PHC) integrates approximately 700 CHWs that once a semester
      visit approximately 110.000 households. In each visit, CHWs contact adults in the household
      and perform health-related tasks including promotion of cervical cancer screening. CHW's
      performance is evaluated annually and classified as good or regular.

      Goals of the study

      A cluster randomized trial will be conducted; it will include a total number of 150-200
      community Health Workers (CHWs) and 6.000 women.

      The aim of this study is:

        1. to assess the self-test effectiveness to increase the participation of women in
           screening programs,

        2. to assess the self-test acceptability by women.

        3. to assess HPV self-test effectiveness for detection of CIN2+ lesions against cytology in
           primary screening.

      Study randomized by population clusters

      An overall number of 150-200 CHWs from the Primary Health Care System (PHCS) of the Province
      of Jujuy will be randomized into two groups: Self-test Group (ST) and Conventional Sample
      Group (CS)

        1. ST Group: CHWs will invite eligible women of their area to choose between doing a
           self-test or having a conventional sample taken by a health professional at the closest
           health care center.

        2. CS Group: CHWs will invite eligible women in their area to have a conventional sample
           taken by a health care professional at the nearest health care center.

      1) Procedures to carry out in each group:

      1.1) Active search

      • Self-test Group:

      During the home visits that CHWs carry during health rounds, selected CHWs will visit every
      household they are in charge of and will invite eligible women to participate in the study,
      providing them with the necessary information about the goals and activities involved.
      Eligible women willing to participate in the study will be invited to sign an informed
      consent. Next, they will be offered the possibility of doing a self-test or to visit a health
      care center to have a sample taken by a health care professional. Women who agree on the
      self-test will be given the option to have more time to do the test if they need so and the
      CHWs will come back later to pick up the collecting tube. CHWs will explain the procedure
      based on the communication material designed for that purpose. Women who decide to be
      screened at health care centers will receive information about available timetables. The CHWs
      will bring the self-taken sample to the health care center, where all collecting tubes will
      be stocked to be sent to the provincial HPV laboratory, according to usual procedures and
      delivery schedules.

      CHWs will update the F883 template, the standard PHC form used by CHWs to collect
      socio-demographic and health data of the household and its members. In addition to that, CHWs
      will use a specific questionnaire to collect basic about inclusion/exclusion criteria,
      self-testing acceptability and reasons for doing/not doing self-testing.

      • Conventional Sample group:

      During the home visits that CHWs carry during health rounds, selected CHWs will visit every
      household they are in charge of and will invite the eligible women to participate in the
      study, providing them with the necessary information about the goals and activities involved.
      Eligible women willing to participate in the study will be invited to sign an informed
      consent. Next, they will be given an education talk promoting cervical screening. They will
      be given information about HPV testing at health care centers as well as educational material
      on the prevention of the disease.

      CHWs will update the F883 template, the standard PHC form used by CHWs to collect
      socio-demographic and health data of the household and its members. In addition to that, CHWs
      will use a specific questionnaire to collect basic about inclusion/exclusion criteria,

      Women from this group, upon visiting the health care center for the conventional test, will
      be taken an HPV and Pap test at the same time, based on the provincial protocols and
      regulation framework. Samples will be sent to be read at the Cytology and HPV Laboratory,
      according to standard provincial mechanisms.

      1.2) Delivery of results, follow up and treatment:

      • Self-test group:

      Women tested HPV positive will receive the visit of the CHW to inform them of the result.
      They will be invited to undergo diagnosis studies (colposcopy/biopsy) at their closest health
      care center. The CHW will brief them on the availability of timetables, professionals and
      health care centers.

      Those women with suspicious colposcopic images will have a targeted colposcopy-directed
      biopsy taken, to be read by the provincial pathological anatomy laboratory.

      Women with histologically confirmed precancerous lesions wil be followed up and treated based
      on the protocols established on the Recommendations for screening, follow up and treatment of
      women for the prevention of cervical cancer in the framework of the HPV test incorporation,
      by the National Ministry of Health20.

      The data about Pap tests, colposcopy, biopsy and treatments will be registered at SITAM
      (screening information system), following the Provincial Program for Cervical Cancer
      Prevention regulation.

      • Conventional sample group:

      Women tested HPV positive, with abnormal Pap test, will be visited by the CHW to inform them
      of the result and invite them to undergo a colposcopy at their closest health care center.
      The CHW will brief them on the availability of timetables, professionals and health care
      centers.

      Women tested HPV positive but with a normal Pap test, will receive the results based on the
      usual procedures set forth by the Provincial Program for the Prevention of Cervical Cancer.

      Those women with suspicious colposcopic images will have a targeted colposcopy-directed
      biopsy taken, to be read by the provincial pathological anatomy laboratory.

      Women with a histologically confirmed precancerous lesion should be followed up and treated
      based on the protocols set forth in the Recommendations for screening, follow up and
      prevention of cervical cancer in the framework of the HPV test incorporation, by the National
      Ministry of Health20.

      The data about Pap tests, colposcopy, biopsy and treatments will be registered in SITAM,
      based on the Provincial Program for the Prevention of Cervical Cancer regulation.

      2. Training for CHWs:

      All participating CHWs will be informed about the study and a special training will be
      provided. During the training sessions, the goals of the study, the main activities to be
      carried out and the specific tasks that each one of them will have to perform will be
      explained.

      3. Production of communications material:

      Informative material will be prepared for CHWs participating in the study, the main goals of
      the study will be explained in it and guidelines with the steps to follow during the home
      visit will be provided to them.

      Similarly, a special leaflet will be prepared with the self-test instructions to be delivered
      to those women to whom that option is offered.

      Besides, all contacted women will be given general leaflets on cervical cancer prevention and
      the HPV Test and those women that did the self-test will be given a leaflet on the meaning of
      HPV Test results.

      4. Sample selection and size

        1. Proposed sample size for the coverage study

           With the purpose of selecting CHWs participating in the study, a list of all the CHWs of
           the province of Jujuy will be made (N = 678). Then they will be classified by gender and
           type of health care center (urban or rural). The CHWs that over the year 2011 have been
           rated of regular performance by the PHC system will be excluded from the study.

           150-200 CHWs will be randomly selected, in a sample proportional to the size of four
           strata defined by gender and health care center type. The CHWs selected in every stratum
           will be randomly allocated to each one of the study groups (half for the Self-test group
           and half for the Conventional Sample group).

           Assuming that a CHW will enroll an average of 40 women (with a minimum target of 20
           women) in the two visits of the round, the overall number of women enrolled in every
           study group will approximately be at least 75 x 40 = 3.000 (number of CHWs x number of
           women per CHW) with a total number of 6.000 women in the study. We assume that the
           coefficient of intra-class correlation (CIC) is 0.05, 0.075 or 0.10 the power to detect
           a 10% change (from 50% to 60%) in the first coverage indicator for a 5% level of
           significance test is 0.999, 0.97 and 0.93 respectively.

        2. Self-test acceptability estimate

           Acceptability is defined as the percentage of women accepting doing the self-test
           against the number of women offered the self-test or the conventional sample option.
           Under the scenario described in the previous section the expected half-length of the 95%
           confidence interval for acceptability within the population is 3.1%, 3.5% and 4.0% for a
           CIC of 0.05, 0.075 and 0.1 respectively.

           These values are dawned considering the worst situation regarding the length of the
           confidence interval, which stems from assuming an acceptability of 50%.

        3. Sample size for the CIN2+ detection rate comparison of the HPV Self-test versus cytology
           as a primary screening method

      We will compare the detection rate of histologically confirmed CIN2+ lesions diagnosed in
      2011 within the framework of the provincial program for the prevention of cervical cancer,
      based on cytology as primary screening method, against the HPV Self-test detection rate
      (relative sensitivity). This analysis will include approximately 20.000 women of 30 years of
      age and older screened with cytology during the year 2011, in the framework of the provincial
      screening program, and the 3.000 women that are expected to be screened by means of the HPV
      Self-test within the framework of the present research project.

      The cytology detection rate for the year 2011 in the province of Jujuy is of approximately
      0.8%. If it is assumed that with the HPV Self-test the detection rate to be reached will be
      of 1.4%, 1.6%, 1.8% or 2.0%, the power of the one-tailed test (5% level of significance) to
      compare the CIN2+ detection rates turns out to be 0.895, 0.977, 0.966 and 0.999 respectively.
      The power calculation was done assuming there is no impact produced by the CHW on the CIN2+
      detection rate.

      5. Database:

      A database built specifically for the study will be used; it will include data about
      randomization Group, agreement to participate in the study, basic socio-demographic data,
      realization of self-test (in the corresponding group), and if appropriate, reasons for
      doing/not doing the self-test. Finally, the HPV Test realization will be uploaded importing
      the data from SITAM, linking data based on the Unique Identification Number (DNI).

      Data entry will be done through specific software that will include range and inter-item
      consistency checks. Entries out of the expected range will not be allowed. Data entry will be
      done by 3 data enters, with re-entry of 20% of questionnaires for quality control. Data will
      be stored in files (TXT, DBF, SQL) compatible with their analysis with statistical packages
      (Stata).

      The data cleaning process will actively search for errors in a planned way. Data screening
      will include searching for four types of oddities: outliers (including inconsistencies),
      strange patterns in distributions, and unexpected analysis results. Screening methods will
      include browsing of data tables after sorting, printouts of variables not passing consistency
      checks, graphical exploration of distribution, frequency distributions and cross-tabulations
      and summary statistics. Once errors have been identified, we will go to previous stages of
      the data flow to see whether the value is consistently the same. If no error is found in the
      data entry phase, we will question the interviewer about what may have happened. If possible,
      we will contact the interviewee for repeated measurement.

      Accuracy of previous HPV test reported by the woman will be crossed with information from the
      laboratory database (SITAM). Those women having reported not having a previous HPV test, but
      with a test in the SITAM data base will be excluded from the study.

      The project database will be also matched with the PHC database. For that purpose, the
      records of women of 30 years of age and older residing in the areas included in the study
      will be imported from the PHCS databases, including name, DNI and basic socio-demographic
      data of the woman.

      Plan for missing data

      Data are exhaustive and complete for all samples arriving to the HPV laboratory. Because we
      define the outcomes as number of tests effectively recorded in the laboratory database
      (SITAM)/ number of women in the study arm, we do not expect to have missing data in the main
      outcome.

      SITAM database is less complete regarding follow-up diagnosis procedures: colposcopy and
      biopsies. In those cases where HPV+ women have missing data for colposcopy and/or biopsy
      results, the project team will contact Navigators from the Provincial Program for Cervical
      Cancer Prevention. Usual navigators´ role in the provincial Program is to contact women with
      abnormal results that have had problems to complete diagnosis/treatment procedures to provide
      them support so they can be able to finish the process. They can also contact health
      professionals to verify information reported by women: for example, in cases where women
      reported having been treated but no data is registered in SITAM. In that case, they contact
      the health professional to verify treatment provided and its results. Information gathered by
      navigators is entered in SITAM in a specific module which will be also used to complete data
      for missing cases.

      6. Data analysis:

      Data analysis will be done through specific commercial softwares (STATA 10.0 or SAS).

      6.1 Self-test acceptability:

      Acceptability is defined as the number of women accepting the self-test against the number of
      women offered the option between the self-test and the conventional sample (proportion of
      women accepting the self-test). Although all CHWs will receive the same instructions and
      material, it is to be expected that there will be differences in the way the self-test is
      offered, be it because they are more convinced about the relative advantages, or for their
      gender condition, etc. The acceptability in this population will be estimated as the average
      of acceptabilities calculated by CHW, as to control the impact of the CHWs on acceptability
      and reach an appropriate variance estimate. Besides, the variability introduced by the CHWs
      on acceptability will be studied and the results obtained by male and female CHWs will be
      compared, as well as those obtained by the CHWs in rural and urban areas.

      6.2 Self-test effectiveness to enhance participation of women in screening and diagnosis:

      There will be a comparison of the percentage of women that did the HPV test in the Self-test
      group and the Conventional sample group. Three different coverage indicators will be
      considered for every CHW. These will be defined as the number of women screened within the
      field work regarding:

        1. The number of women reached by the CHW who accepted participating in the study.

        2. The number of eligible women for that CHW (regardless of whether the CHW was able to
           contact them or not).

      For every CHW we will measure the adherence to the indication of follow up diagnosis as well
      as the number of women with colposcopy indication that underwent a colposcopy within the
      follow-up period over the overall number of women with colposcopy indication.

      The effect of the strategy (offering the self-test option against promotion of the
      conventional sample) will be estimated for each one of the coverage measures using a means
      difference test or a non-parametric test for independent samples.

      6.3 CIN 2+ detection rate:

      The effectiveness of the HPV Self-test against screening cytology to detect CIN2+ will be
      estimated as the detection rates difference and as the detection rates ratio. Specific
      estimates will be provided as well as intervals of confidence for both measures of
      effectiveness and accurate or asymptotic tests will be performed as appropriate based on the
      number of CIN2+ detected.

      In addition, there will be a comparison of the CIN2+ detection rate in the group of women who
      did the self-test against the total number of women in the province of Jujuy that were tested
      for HPV (conventional sample strategy + triage Pap test) until December 2012. The power of
      the comparison for the difference observed will be informed upon reporting the results.
    


Study Type

Interventional


Primary Outcome

Screening Uptake

Secondary Outcome

 Acceptability

Condition

Cervical Intraepithelial Neoplasia

Intervention

HPV self testing

Study Arms / Comparison Groups

 HPV Self testing
Description:  HPV self testing offered by CHWs during home visits

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

6013

Start Date

July 2012

Completion Date

December 2013

Primary Completion Date

January 2013

Eligibility Criteria

        Inclusion Criteria:

          -  woman aged 30 or older

          -  lived in a household visited by one of study CHWs

        Exclusion Criteria:

          -  hysterectomy

          -  been treated for a precancerous lesion

          -  with previous HPV test

          -  pregnant

          -  mentally-disabled.
      

Gender

Female

Ages

30 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Silvina Arrossi, PhD, , 

Location Countries

Argentina

Location Countries

Argentina

Administrative Informations


NCT ID

NCT02095561

Organization ID

01-1CU


Responsible Party

Principal Investigator

Study Sponsor

Instituto Nacional del Cáncer, Argentina

Collaborators

 Ministerio de Salud de Jujuy

Study Sponsor

Silvina Arrossi, PhD, Principal Investigator, National Council of Scientific and Technical Research, Argentina


Verification Date

August 2020