Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Infections

Immune System Diseases

Symptoms and General Pathology

Uterine Cervical Neoplasms

Acquired Immunodeficiency Syndrome

HIV Infections

HIV Seropositivity

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Communicable Diseases

Blood-Borne Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Lentivirus Infections

Retroviridae Infections

Virus Diseases

RNA Virus Infections

Syndrome

Immunologic Deficiency Syndromes

Claire FIEVRE

The main objective of this study is to evaluate the interest of a screening strategy based on the HPV test in patients living with HIV, compared to the cell smear alone in the same population.

The Secondary objective of this study is to verify if the use of HPV testing could allow for a longer follow-up of these patients in case of negativity, and thus allow for a standardization of clinicians' practices.

Since 2019, a new screening strategy has been implemented and is based on high-risk, HPV tests, which, when negative, allow for spaced monitoring in the general population after age 30 (every 5 years instead of every 3 years.)

These tests therefore allow for earlier detection of patients at risk but also for longer follow-up when they are negative.

To our knowledge, there is currently no evaluation of HPV testing as part of routine screening in patients living with HIV.

The recommendations for this population are based on the use of the cervico-vaginal smear with cytological analysis. The smear should be taken every year and surveillance may be repeated every 3 years. If there are 3 consecutive smears without abnormalities and a controlled viral load with CD4 counts \> 500 mm3. In practice, many patients do not meet these criteria and must, therefore, undergo annual screening; the increase in the number of smears also leads to an increase in the number of second-line examinations such as colposcopy.

Since there is no recommendation for HPV testing in this population, the use of dual detection (cytology and HPV testing) is left to the discretion of the clinician.

By mutual agreement with the clinicians of the maternity department of the Saint-Denis Hospital (CHSD), this double detection was introduced in 2021, using the same sample (single swab for both analyses: cytology and HPV test).

Therefore, it seems interesting to verify the possibility of a screening strategy based on HPV testing in patients living with HIV, by correlating the results of HPV testing and cell smears in the population of patients living with HIV.

The Value of HPV Testing for Cervical Cancer Screening in Women Living With HIV (PAPILLO-VIH)

The Value of HPV Testing for Cervical Cancer Screening in Women Living With HIV

Results of any additional examinations prescribed

Centre Hospitalier de Saint-Denis

Papillomavirus Infections

DNA Virus Infections

Tumor Virus Infections

Disease Attributes

All women over 30 years of age who are not participating in screening or have not had a screening visit in less than 5 years.

All women over 30 years of age who regularly participate in screening but have not had an HPV test in the last 3 years.

HPV DNA swab from the cervix performed by the patient herself.

HPV DNA self-test

Jiří Sláma, MD, PhD

Lucie Panýrová, PhD

Jiří Sláma, MD PhD

Lucie Mandelová, PhD

Veronika Cibulová, MS

One of the limitations of organized cervical screening in the Czech Republic is the lack of participation in preventive gynecological examinations. The aim of the project is to evaluate the benefits of self-sampling for HPV DNA in general practitioners' outpatient clinics to improve population participation in cervical screening.

Organized cervical screening in the Czech Republic has a long-term participation rate of about 56% of the target population. Despite active invitations through health insurance companies, a part of the population is resistant and does not participate in screening visits to gynaecologists in the long term. A significant proportion of such women, however, regularly visit their general practitioner due to other comorbidities. The aim of the ASTRA project is to assess whether an effective way to increase the proportion of women attending cervical screening is to perform self-testing for HPV DNA in the GP's office.

HPV DNA Self-sampling in a General Practitioner's Office.

Benefit of Self-sampling for HPV DNA in a General Practitioner's Office to Improve Participation in Cervical Screening - The ASTRA Study.

To compare the proportion of women who self-test for HPV DNA in a GP office versus those who refuse to take the test. To assess the overall proportion of women who self-test and the proportion in each study cohort.

Compare the proportion of women who will self-test positive for HPV DNA, including an assessment of positivity for HPV 16/18 and other HPV genotypes. To assess the overall proportion of women testing positive and the proportion in each study cohort.

To assess what proportion of women who self-test positive for HPV DNA will accept a gynecologic exam and to assess the results of the gynecologic visit.

Patient Organization Veronica

Pharmaceutical Solutions

All Drugs and Chemicals

Anti-Infective Agents

Fenbendazole

Patients received colposcopy as per standard of care

Women will undergo colposcopy at 6 and 12 months after randomization. Those with CIN II will be managed according to standard of care. Those with CIN 1 6 months post randomization will have a second exam 6 months later and if still CIN I will have an exit colposcopy 6 months later.

All women in the Pap and HPV testing policies as well as all women in the colposcopy policy with CIN 1 after 2 exams will have an exit colposcopy 18 months after randomization. The exit colposcopy is a safeguard against the possibility of any false negatives in the follow up policies. The exit colposcopy will also establish the true numbers of CIN lesions in the 3 policies in order to determine their sensitivities and specificities. At the exit colposcopy,all will have an endocervical curettage,and either a minimum of 2 directed biopsies of any mucosal abnormality or in the event no abnormality is identified,2 random biopsies from the cervix.

Colposcopy

Women will receive Pap tests at 6 and 12 months after randomization. The Pap test will be prepared using the Thinprep® system which is the standard at Calgary Laboratory Services. Women with a Pap test result of malignant, HSIL, AIS, AGC, ASC-H, or LSIL-H (\>LSIL) at 6 or 12 months post randomization will be referred for colposcopic examination. Women with an ASC-US or LSIL result (\</=LSIL) will have a second follow up Pap test 6 months later (12 months post randomization). Those with a persistent result of ASC-US or LSIL or \>LSIL at 6 or 12 months will be referred for colposcopic examination. Outcome in the Pap policy is positive when the histopathology is \>/=CIN II. Results of \</=CIN I equal a negative outcome.

All other Pap test results will have an exit colposcopy 6 months later (18 months post randomization).

Pap test

Women will have an HPV test performed on a cervical scrape sample 12 months after randomization. Women with a positive result will be referred for colposcopy. Outcome in the HPV testing policy is positive when histopathology obtained at the colposcopic exam shows CIN II. All other results equal a negative outcome. HPV negative women will have an exit colposcopy 18 months post randomization. HPV testing will be performed using Cervista™HPV HR(Third Wave Technologies Inc./Hologic Inc, Madison, WI, USA).This HPV DNA test identifies 14 high risk types (16,18,31,33,35,39,45,51,52,56,58,59,66,68). Testing will be performed on the residual cervical scrape sample which is fixed in the PreservCyt® solution of the Thinprep® liquid based system(Hologic Inc, Marlborough, Ma, USA). Cervical samples may be held for up to 24 wks at room temperature before DNA extraction.This allows time for transportation without refrigeration.The samples will be sent by overnight express delivery to the laboratory.

HPV test

Gregg Nelson, MD, FRCSC, PhD

There is weak evidence supporting optimal follow-up of women with ASC-US or LSIL cytology found to have low grade disease or normal findings at initial colposcopy. Surveillance options include continued colposcopy, discharge with Pap testing, or HPV testing at 12 months. The investigators performed a pilot randomized controlled trial (RCT) comparing these 3 follow-up policies. Study objectives are to determine the feasibility of an RCT and to compare the incidence of \>/=HSIL in each of the arms by intention to treat principle.

1. BACKGROUND In 2010 the estimated age standardized incidence and mortality rates for cancer of the uterine cervix in Canada were 7 and 2 per 100,000 women respectively. Squamous cell carcinoma is the most frequent type and arises from a premalignant squamous dysplasia called cervical intraepithelial neoplasia (CIN). There are 3 grades of CIN from I to III in order of increasing severity. A systematic review of 73 studies on the natural history of CIN, determined nearly 89% of CIN I regressed to normal or a benign lesion or persisted unchanged, and progression to CIN III occurred in 11% and to cancer in 1%. In contrast, CIN III and II had a greater malignant potential as 12% and 5% respectively progressed to cancer. The low incidence and mortality rates of cervical cancer are largely attributed to the availability of screening for CIN with the Pap test (Papanicolaou stained cervical smear) and the colposcopic management of cytologic abnormalities. While rates have plateaued in recent years, decreases are expected with additional improvements in Pap test performance and pre-colposcopy management of cytologic abnormalities. Changes to the post-colposcopy management of cytologic abnormalities could also improve the rates, but rigorous investigation of potential changes is lacking.

1.1 Management and outcome of cytological abnormalities The Bethesda System (TBS) is the recommended Pap test reporting terminology in Canada. TBS 2001 classifies results as negative for intraepithelial lesion or malignancy (NILM), or an epithelial cell abnormality. The latter includes 1) atypical squamous cells of undetermined significance (ASC-US), 2) atypical glandular cells (AGC), 3) low grade squamous intraepithelial lesion (LSIL), 4) atypical squamous cells, cannot exclude HSIL (ASC-H), 5) high-grade SIL (HSIL), 6) adenocarcinoma in situ (AIS), and 7) malignant.

Management of cytological abnormalities may involve colposcopic examination. The colposcope magnifies the cervix and allows directed biopsy of any visualized mucosal abnormality (impression). A repeat Pap test and tissue sampling of the endocervical canal (endocervical curettage; ECC) can also be carried out. CIN II, III and cancer diagnosed at the first colposcopy exam are considered to be incident disease undersampled by the referral Pap test (incident \>/=CIN II) 3. CIN II or higher detected within the subsequent 24 months is categorized as progressive disease. Some investigators however, also consider it incident disease that escaped earlier colposcopic detection and refer to incidentally detected and progressive CIN II or higher as cumulative CIN II (CIN 2+).

Approximately 1% of cytological results in the United States is an HSIL, 4.4 % is an ASCUS (atypical squamous cells of undetermined significance to include ASC-US and ASC-H) and 1.6% an LSIL. Canadian data is somewhat similar (Calgary Laboratory Services unpublished quality assurance data), Since upwards of 60-80% of HSIL is a CIN II/III colposcopic examination and treatment is appropriate so as to prevent cervical cancer. Uncertainty and controversy in regard to the outcome of ASC-US and LSIL existed until the completion of the ALTS (ASCUS and Low Grade Triage Study) randomized clinical trial. The trial determined 13% of the combined ASCUS and LSIL cohorts had an incident \>/=CIN II and an additional 8% progressed to CIN II/III. These results underscored the importance of managing low grade cytological abnormalities to prevent cervical cancer.

1.2 Pre-colposcopy management of ASC-US and LSIL Current management of ASC-US and LSIL in Canada is guided by the Clinical Practice Guidelines of the Society of Obstetricians and Gynecologists of Canada (SOGC) and the 2001 and 2006 guidelines of the American Society for Colposcopy and Cervical Pathology (ASCCP). Management options include referral to colposcopy after a single or double test result of ASC-US or LSIL or a single ASC-US result testing positive for HPV (Human Papilloma Virus) DNA (deoxyribonucleic acid). Management in Canada is mostly based on repeat Pap testing since HPV testing is not routinely available in every jurisdiction. For example, in Alberta, 2 years of repeat Pap testing carried out at 6-month intervals is the standard for an ASC-US or LSIL detected during routine screening and referral to colposcopy occurs when follow up Pap tests show persistence or progression.

1.3 Colposcopy management of ASC-US and LSIL Mucosal abnormalities of the cervix are biopsied and additional treatment is based on the histopathological results. Repeating the Pap test at colposcopy is of minimal value in the added detection of CIN II/III/cancer, and is not routinely performed. An ECC is recommended to sample disease in the endocervical canal. ASC-US and LSIL tests with incident \>/=CIN II are treated with ablation or excision, whereas those with \</=CIN 1 (benign/CIN I) are not treated.

1.4 Post-colposcopy management of ASC-US and LSIL The post colposcopy management of women referred with ASC-US or LSIL and who do not have incident \>/=CIN II is still uncertain. Management algorithms are available from the ASCCP despite the absence of strong evidence to support all of the recommendations. Amongst those with \</= CIN I at colposcopy, a repeat Pap test at 12 months is recommended if the women were referred with ASC-US and the HPV DNA status at colposcopy was unknown, and repeated at 6 and 12 months if they were referred with an HPV positive ASC-US or an LSIL. HPV DNA testing at 12 months is an option for those referred with an HPV positive ASC-US or an LSIL. Women would be referred back to colposcopy if the repeat Pap test was ASC-US or higher or the HPV DNA test was positive. The evidence was rated BII and BIII by the ASCCP which they defined as "moderate evidence for efficacy or only limited clinical benefit supports recommendation for use (B); based on evidence from at least one clinical trial without randomization, from cohort or case controlled analytic studies, or from multiple time series studies, or dramatic results from uncontrolled experiments (II); evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees (III)".

Post-colposcopy management of ASC-US and LSIL in Canada is very variable and likely reflects the lack of strong evidence supporting the existing guidelines. Based on 102 survey responses from 252 Canadian colposcopists, 43% recommended discharge from colposcopy for ASC-US/LSIL negative for CIN, while 53% recommended repeat colposcopy. For ASCUS/LSIL positive for CIN I, 13% recommended discharge to Pap test follow-up, 65% recommended repeat colposcopy, and 16% recommended treatment. The number of follow up colposcopy exams was variable but there was at least one at 6 months and more often a second at 12 months. The survey highlighted a greater reliance on colposcopy as a standard of follow up care and a reluctance to discharge women for follow up with routine Pap tests performed in the primary care setting. Notably, no participant reported utilizing HPV DNA testing. The high (48%) level of survey participation and individual participant's comments attested to the community's interest in scientifically evaluating the best post-colposcopy management strategy for this clinical scenario.

1.4 Post-colposcopy management of ASC-US and LSIL negative for incident CIN II/III The ALTS trial was principally designed to assess the pre-colposcopy management of women with ASCUS or LSIL. Later, some of the trial data was used to test repeat cytology and HPV testing as post-colposcopy management options. Repeat colposcopy examination could not be measured as a management option. HPV testing at 12 months was found to be 92% sensitive for progression to \>/=CIN II amongst those with \</=CIN I at the initial colposcopy and would refer 55% of women back to colposcopy. The sensitivity compared very well with the 88% obtained with 2 follow up ASCUS Pap tests which however would refer slightly more (64%) women back to colposcopy. The sensitivity of a single colposcopy exam for cumulative CIN II is generally considered to be approximately 80% but may be closer to 55% based on recent data from the ALTS trial. Thus post colposcopy follow up with a single HPV test at 12 months or repeat Pap testing at 6 and 12 months may be equivalent to or more sensitive than follow up with 1 or even 2 colposcopy exams. However, a randomized trial is needed to prove this hypothesis and provide the evidence needed to change the current colposcopy dominated practice in Canada.

2 RESEARCH DESIGN This is a pilot randomized controlled trial performed at the Holy Cross Colposcopy Clinic of the Calgary Health Zone for the purpose of testing a randomized clinical trial which will be designed to test above-stated objectives. The pilot will test the recruitment, randomization, operational feasibility, and clinical outcomes. The pilot data will be added to the future full proposal of the clinical trial. Potential additional studies stemming from the clinical trial will include the evaluation of molecular determinants of outcome, e.g. persistence of specific HPV types, viral load and viral integration, analyses of temporal changes in behavioral factors, and cost effectiveness of the 3 arms.

3 RESEARCH METHODOLOGY 3.1 Pilot sample, enrolment and randomization

Usual colposcopic and pathology practices will be applied at the initial exam and a repeat Pap test will not be performed. After enrolment, baseline data will be extracted by the study team from the clinic charts, including date of the referral Pap test and result, date of the colposcopy exam, colposcopy impression, and cervical biopsy and ECC results. Those with \</=CIN I by impression and pathology will not be treated. These women will be randomized by RANDOMIZE.NET to one of the 3 follow up policies - colposcopy (considered standard of care), cytology or HPV testing (simulating discharge to community). A sticker will be added to the clinic charts describing the woman's policy.

All cervical disease identified at these referrals back to colposcopy will be managed in accordance with standard protocols.

4 DATA MANAGEMENT AND ANALYSIS 4.1 Data management All data collected by the research team will be collected in a de-identified fashion in the REDCap Software managed by University of Calgary. Data discrepancies will be reviewed by an independent third person. Data forms will be checked prior to data entry, and range and logic checks carried out regularly on entered data to ensure the quality of the data. Any results that appear to be out of range or do not comply with the logic checks will be checked with the hospital or clinic case notes and the woman and her clinician.

4.2 Data analysis Patient demographics and characteristics will be reported using descriptive statistics, and comparisons between the three arms will be done using the Chi-square test or Fisher's exact test for categorical variables and the Kruskal-Wallis test for continuous variables. For the primary outcome, the investigators will report the proportion of high risk disease along with the 95% confidence intervals, and compared the arms using relative risks and 95% confidence intervals, with the Colposcopy arm as the reference group. Sensitivity, specificity, positive predictive value, and negative predictive value will be calculated in each arm. SAS 9.3 (SAS Institute Inc., Cary, NC, USA) will be used for analyses. Non-inferiority of repeat Pap and HPV testing follow-up policies strategies, relative to colposcopy is hypothesized. Inferiority will be defined as the smallest relative disadvantage in sensitivity that would be of practical clinical interest. Investigators assume this margin to be less than 1% based on informal discussions with colposcopists in Calgary and in the absence of relevant publications.

Post Colposcopy Management of ASC-US and LSIL Pap Tests

Post Colposcopy Management of ASC-US and LSIL Pap Tests (PALS Trial): Pilot Study

Adherence will be defined as colposcopist performing the test the patient is randomized to and NOT performing a different test. Proportion of patients who had the correct test done over total number of patients being tested will be recorded.

Percentage of eligible patients will be calculated by counting the number of referrals to colposcopy with eligible cytology over total number of referrals; patient participation rate will be calculated by counting the number of eligible patients over number of patients consenting to participate in the study

Determine the incidence of \>/=HSIL (CIN 2/3) in the study population

University of Calgary

Vaginal specimens for HPV test will be collected by participants themselves using flocked swabs after explanations by co-investigators. Two transport mediums will be used for those self-collected vaginal samples: NaCl 0.9%.

HPV Test

In sub-Saharan Africa, cervical cancer is the leading cause of cancer death among women because of the difficulty in implementing screening programs. The main obstacles in these countries are poverty, lack of healthcare infrastructures and trained practitioners. With the availability of new technologies, researchers are looking for new strategies adapted to low- and middle-income countries to identify cervical precancerous lesions.

Current evidence shows that Human Papilloma Virus (HPV) testing is more effective than cytology (Pap smear) for cervical cancer screening in resource-limited settings. Indeed, the GeneXpert® HPV test offers the opportunity to prevent cervical cancer (CC) in a single visit: rapid detection of high-risk HPV (HPV) infection followed by same day treatment of HPV-positive women during the same visit (screen-and-treat approach).

However only a small proportion of HPV-positive women will develop cervical (pre)cancer, making it important to select those to treat. This triage can be achieved by colposcopy, cytology and visual inspection after application of acetic acid (VIA). Though VIA is the triage test recommended by WHO for resource-limited countries, it has not yet been widely assessed in sub-Saharan Africa (SSA).

The main objective of the investigators is to assess the performance of HPV-test followed by Visual Inspection after application of Acetic acid and Lugol's iodine VIA/VILI to detect cervical precancerous lesions in a screen-and-treat strategy in Cameroon (sub-Saharan Africa) where there is no cervical cancer-screening program.

The investigators organized a successful free screening campaign in Cameroon in 2015 that allowed to identify the expectations of women and their eagerness to benefit from prevention of gynecological cancers and sexually transmitted diseases.

Only women will be recruited by the study

Promoting Comprehensive Cervical Cancer Prevention and Better Women Health in Cameroon

VIA/VILI is assessed by pelvic examination and Sensitivity and specificity are measured by using histology as gold stantard

HPV self-test analysed by GeneXpert machine

Histological analyses of cervical biopsies and endocervical brushing

Measured by self HPV performed at 6 and 12 months follow up

To assess the acceptability of self-HPV, patients complete a questionnaire comprising different questions about the collection device (embarassment, comfort, anxiety and confidence about the test).

Likert Scale 4 points : 1 (not at all) to 4 (very).

VIA/VILI is assessed by pelvic examination

Thermal ablation efficacy rate will be assessed according to the biopsy proven CIN2+ rate after thermoablation treatment at the 6 and 12-month follow-up. The absence of CIN2+ will determine the success of the treatment in a patient who previously had a CIN2+ lesion.

Adverses event : bleeding, complications, hospitalization

To assess the acceptability of thermoablation, patients completed a questionnaire comprising different questions about treatment tolerance, pain and following side effects. Respondent were invited to rate answers on a likert scale of 1 (no accpetability) to 4 (high acceptability)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Value of HPV Testing for Cervical Cancer Screening in Women Living With HIV (PAPILLO-VIH)	NCT05968183	HIV Seropositiv...		25 Years - 65 Years	Centre Hospitalier de Saint-Denis
HPV DNA Self-sampling in a General Practitioner's Office.	NCT06253169	Cervical Cancer HPV Infection Precancerous Le...	HPV DNA self-te...	30 Years -	Patient Organization Veronica
Post Colposcopy Management of ASC-US and LSIL Pap Tests	NCT03466710	Cervical Cancer...	Colposcopy Pap test HPV test	18 Years -	University of Calgary
Promoting Comprehensive Cervical Cancer Prevention and Better Women Health in Cameroon	NCT03757299	Cervical Cancer	HPV Test	30 Years - 49 Years	University Hospital, Geneva

Spots Global Cancer Trial Database for hpv test

Every month we try and update this database with for hpv test cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hpv test

Every month we try and update this database with for hpv test cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hpv test cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.