Infections

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Communicable Diseases

Papillomavirus Infections

Vaginal Discharge

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Genital Diseases

Urogenital Diseases

Disease Attributes

Vaginal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

We enroll a total of 1,200 women, as follows,

1. 120 cases with no history or current cervical intraepithelial lesion or malignancy.
2. 180 cases with a history of abnormal Pap test including ASCUS, CIN1, or atypical glandular cell.
3. 240 cases with a history of atypical squamous cells favor HSIL, dysplasia cannot exclude HSIL, CIN2, CIN3, cervical carcinoma in situ, squamous cell carcinoma, atypical glandular cells favor neoplasm, adenocarcinoma in situ, or cervical adenocarcinoma.
4. 240 cases with current ASCUS, CIN1, or atypical glandular cell.
5. 420 cases with current abnormal Pap test as atypical squamous cells favor HSIL, dysplasia cannot exclude HSIL, CIN2, CIN3, cervical carcinoma in situ, squamous cell carcinoma, atypical glandular cells favor neoplasm, adenocarcinoma in situ, or cervical adenocarcinoma.

A device to collect exfoliative cells from vaginal fornix that can self-operated with ease and comfort.

Self sampling kit for collecting discharge from vaginal fornix

Hung-Hsueh Chou, MBBS, VS

Hygeia Touch Inc. developed a safe and comfortable vaginal self-sampling device "Hygeia Touch Self Sampling Kit for Women" to self-collect the vaginal discharge sample for high-risk Human Papillomavirus (hrHPV) detection.

This clinical trial aimed to evaluate the agreement of hrHPV detections between vaginal self-sampling using "Hygeia Touch Self Sampling Kit for Women" and physician sampling, and these results will be applied for TFDA registration approval.

Primary end-point:

1. Agreement of hr-HPV types, including types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68, between the physician-collected sample and self-collected sample
2. Agreement of the presence of hr-HPV between the physician-collected sample and self-collected sample

Secondary end-point:

1. Percentage of the valid sample between self-collected and physician-collected specimens
2. Agreement of all (N = 27) HPV types between the paired samples
3. Adverse events associated with sample collection
4. Questionnaire of the appreciation and satisfaction of using self-collecting vaginal discharge sample using "Hygeia Touch Self Sampling Kit for Women" through a short movie and a brief illustration
5. Correlation between histological diagnosis and HPV types

Two samples were collected, one by the study investigator using a cervical swab and another one by the patient using the study device immediately after viewing the instruction video and illustration. The association of the self-collected sample and the physician-collected sample was blinded to the laboratory personnel.

the specimen was marked by code which was intended to mask the sample pairing

Detection of HPV in female genital tract.

Agreement of hrHPV Type Between Self-collected Sample From Vaginal Fornix and Physician Collected Sample From the Cervical Surface

Evaluate the Agreement of High-risk Human Papillomavirus Type Between Self-collected Vaginal Discharge Sample Using "HygeiaTouch Self Sampling Kit for Woman" and Physician Collected Sample From the Cervix

Rate of the "agreement". The "agreement" is defined as either (1) presence of any high-risk HPV type in physician collected specimen, and the patient sampled specimen, or (2) absence of high-risk HPV in physician collected specimen and the patient sampled specimen.

Rate of the "agreement". The "agreement" is defined as either (1) presence of any HPV type in physician collected specimen, and the patient sampled specimen, or (2) absence of any HPV in physician collected specimen and the patient sampled specimen.

Percentage of the presence of the beta-globin gene. The ratio could be calculated between self-collected and physician-collected specimens.

The number of participants with any adverse event.

Hygeia Touch Inc.

Neoplasms

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Cervical Diseases

Uterine Diseases

Urogenital Neoplasms

An invitation to order a HPV self sampling test through an online application will be sent by SMS or electronic letter.

2019-2021 - A Cobas PCR Female swab sample packet will be sent. Response rates (participation) will be measured.

2022 and onwards - A FLOQSwab and corresponding sample tube for analysis on the BD COR platform will be sent.

Sending of screening summon.

Miriam Elfström, PhD

Helena Andersson, PhD

Viviann Mattsson, MD

Christer Borgfeldt, MD, PhD

Katarina Kylebäck, MD

Mirjam Våtz, Midwife

Hanna Milerad, MD

Lovisa Bergengren, MD, PhD

Prevention of cervical cancer with cervical screening is one of the most successful screening activities in medicine. In Sweden, screening was implemented in the 1960s and has since prevented tens of thousands of women from having cervical cancer. Individual invitations to screening result in increased attendance therefore evaluating strategies for reaching women through invitations is particularly valuable. Women who regularly attend screening following an invitation reduce their risk of cervical cancer by as much as 90%. Of the women who are diagnosed with cervical cancer (about 550 women per year in Sweden), as many as 38% did not participate in the screening. Invitations for screening are sent to the entire population in Sweden aged 23-70. The current coverage of screening is 82.9%, which represents the proportion of women ages 23-70 who attend according to recommendations. In addition, many women are sporadic attenders who reduce their risk for cancer somewhat. The highest cancer risk is seen among those women who have never participated as well as women who have had a history of precancerous lesions or HPV infection but have not been followed-up. Cervical cancer is the first form of cancer for which there are approved molecular screening tests (HPV test). Unlike the older screening method (cytology), self-collected samples can be analyzed for HPV (the analysis method is so sensitive that it does not matter if the sample is not optimally taken).

Invitations and reminders about cervical screening are sent by letter to the woman's home address (about 3 million letters per year in Sweden). This strategy results in a waste of resources and has a negative environmental impact. Regarding reminders, we have seen in previous research that the effect is not optimal. When sending a physical reminder letter to women who have not participated in more than 10 years (current routine), only 2% of the women invited came for sampling. Reminders with SMS are now standard for many businesses in society, such as car testing or dental appointments. It is inexpensive, saves the environment and there are studies that suggest it is more effective than sending physical letters. In this study, we intend to investigate whether SMS reminders, electronic letters, and physical letters for screening lead to increased participation and thus to a higher proportion of detected, treatable precursors of cervical cancer compared to before.

Non-participation in the cervical screening program and sub-optimal follow-up after abnormalities or infection with a highly oncogenic HPV type detected in screening are the main risk factors for cervical cancer. Given this, It is important to reduce barriers to screening and facilitate participation in the screening program of cervical cancer. Offering self-sampling kits for human papillomavirus (HPV) testing has been examined in several research studies as a way to reach women who have not responded to screening invitations. Women who have been lost to follow-up can also be reached with self-sampling.

The purpose of this study is to investigate whether SMS reminders and electronic letters for screening attendance will increase participation compared to the current method where reminders are sent out with physical letters. In this study, women a with high risk of developing cervical cancer, due to not fully participating in screening or being followed up optimally, will be invited. Women are identified through registry linkages annually that examine screening history and status using a risk algorithm. Women receive an SMS or an electronic letter with an offer to request a self-sampling kit via the internet. Women with a higher risk for cervical cancer can be offered a self-sampling kit sent directly to their home address. The self-sampling kit comes with an instruction on how to take the sample and a postage-free answer envelope.

Submitted samples are analyzed with an approved and accredited method (Cobas 4800, Roche) that analyzes for HPV 16, HPV18 and other oncogenic HPV types. As the screening program changed the accredited HPV test in 2022 (to BD Onclarity), that test will be used from the timepoint of the change and onwards.

In the pilot of the study, follow-up is defined as follows:

1. For those women who are at the highest risk (previous glandular cell changes without follow-up), all HPV-positive women are referred via SMS directly to a women's clinic for investigation. HPV-negative women in this group have no increased risk and receive a text message with a calming message.
2. Women of an age above the screening program but who have either had a cell change that is not followed up or who have not participated at all in the last 10 years are treated in the same way as in paragraph 1.
3. Finally, the women of screening age who have not taken a cell sample for more than 15 years are identified. This group receive an SMS and HPV-positive women are referred, via SMS, for renewed sampling by a specially trained so-called dysplasia midwife. The sample is now being analyzed for both cytology and HPV. If the woman is HPV positive in both tests and in the case of deviating cytology, the woman is referred to a women's clinic. In other cases a text message with a reassuring message is sent.

The study has the usual level of confidence (p \<0.05 two-sided) and statistical power (80%) the ability to demonstrate an increase of participation by 3 times or more.

The protocol was piloted in the Region of Skåne in 2019 and then rolled out nationally in 2020.

The study is rolled out nationally with annual linkages to identify women with an excess risk for cervical cancer and an adaptive approach to reaching women with SMS, electronic letters, and physically letters with direct delivery of HPV self-sampling kits or an option to order a self-sampling kid (depending on risk). The study is coordinated centrally and each region has a contact person to whom women who need follow-up are referred.

SMS-based Summons in Cervical Screening

Can SMS-reminders Result in Increased Participation in Cervical Screening?

Participation rate in screening after summons.

Cytologically and histopathologically confirmed percursors of cervical cancer.

Histopathologically confirmed cervical cancers.

Region Skane

Karolinska Institutet

Affiliated Researcher

A Cobas PCR (polymerase chain reaction) Female swab sample Packet will be sent directly to women with a study invitation letter and instructions. Response rate will be measured.

An invitation to order a Cobas PCR Female swab sample Packet through an online application will be sent. Response rates will be measured.

An invitation to call the coordinating midwife with questions and concerns regarding screening will be sent. The coordinating midwife can help the participant order a Cobas PCR Female swab sample Packet or book a standard screening visit, if desired. Response rates will be measured

The standard, annual renewed invitation to cervical screening will be sent (control, routine practice). Response rate will be measured as a baseline.

The cobas® PCR Female Swab Sample Kit is used to collect and transport vaginal swab specimens self-collected.

Cobas PCR Female swab sample Packet

The standard, annual renewed invitation to cervical screening.

Routine practice

Joakim Dillner, MD

The main purpose is to develop and test an IT-infrastructure to provide more individualized ways of inviting and reaching women who have not participated, despite having been invited with annual reminders, in cervix cancer screening program during a ten year period.

BACKGROUND Non-participation in the screening program is the main risk factor for cervical cancer (Andrae et al JNCI, 2008). Therefore it is important to reduce barriers to screening and facilitate participation in the screening program for cervical cancer. Offering self-sampling kits for human papillomavirus (HPV) testing has been examined in several research studies as a way to reach women who have not responded to screening invitations.

Results from a population-based, randomized study in western Sweden concluded that by offering HPV self-sampling kits to screening non-attendees, 17% of cervical cancer cases could be avoided. Offering self-sampling kits to women who have not attended screening in the organized program, can lead to greater participation without substantial increases in the overall health care costs. While there is a growing body of evidence supporting the use of self-sampling, it is unclear how this strategy can be implemented effectively in the context of an organized screening program. An alternative is to offer women the chance to speak with a coordinating midwife who can answer questions and address concerns regarding screening. It is unclear how the results of different research studies should be put into practical use within an organized screening program. Currently, women who have not attended screening are sent an annual reminder invitation. We want to examine whether these alternative strategies (self-sampling and contact with a midwife) may work as well, or better, than current strategy of reminder invitations to non-attenders.

AIM The aim of this randomized health services study is therefore both to test the feasibility of providing alternative strategies instead of the customary reminder invitations to women in Stockholm (so-called feasibility study, primary aim), and whether such strategies will increase overall participation in screening (secondary aim).

STUDY DESIGN AND METHODOLOGY A new IT infrastructure for ordering a self-sampling kit has been developed by LabMed, KI. This in conjunction with the screening database, will be used to identify and invite women who are long-term non-participants in cervical screening. Women who have not participated for ten years, despite annual reminder invitations, will be identified and randomized to one of four strategies.

1. A validated HPV self-sampling kit will be sent directly to women with a study invitation letter and instructions.
2. An invitation to order an HPV self-sampling kit through an online application will be sent.
3. An invitation to call the coordinating midwife with questions and concerns regarding screening will be sent.
4. The standard annual reminder invitation will be sent (control, routine practice)

Women who choose to participate will be sampled and monitored according to the standards of care in the regional cancer screening program. HPV-positive women will be followed by colposcopy and biopsy according to standard clinical guidelines. Women will be invited over the course of 3 months. All letters will be printed in advance with pre-marked dates. Batches will be sent out weekly and checked against changes in the population registry data (for individuals that have moved, taken a smear, died, or unregistered, invitation letters will be sorted out and those individuals marked in the database).

2 Notation and abbreviations

* PNR = person nummer, personal ID number 3 Study population 3.1 Inclusion criteria
* Women who have lived in Stockholm for the past 10 years and have been sent annual reminder at least once per year for 10 years without attending screening.

Specific selection process:

Include women without an "H-prov" on record for the past 10 years Include women have actively been sent a reminder invitation (invitation type=1) during 10 years time. In other words, resident in Stockholm for the past 10 years.

Include women over the age of 33 3.2 Exclusion criteria Women who have opted out of the screening program Hysterectomized Return to sender Changed PNR Women who are marked as Expired=1. Women who have reason marked for being unregistered but are not marked as is unregistered=1.

Women who are due to receive their reminder invitation in the next 3 months 4 Statistical analyses Selection of the study population Randomization A random selection of 8000 women will be chosen from all women meeting the study inclusion criteria.

These 8000 women will be randomized to the 4 study arms (age-stratified 30-50 and 51-60).

The selection of the study population and the randomization to study arms will be carried out by Anna Stoltenberg, Statistician at RCC and outside of the study group 1.

Follow-up - study end date 2016-12-31

IT-system Development for Reaching Cervix Cancer Screening Non-attenders

IT-system Development for Individualization of Cervix Cancer Screening and Implementation of New Strategies to Reach Non-attenders

Our intention is to share data, but a plan for how this will be done in practise has not been written.

Regional Cancer Centre Stockholm Gotland

Professor

Pharmaceutical Solutions

All Drugs and Chemicals

The women will receive the usual recall with a new invitation letter with a prefixed appointment.

Dry one, where FloqSwab, with which perform the sampling is contained and will be preserved after sampling in a tube without preservation solutions

Wet one in which, after sampling, the FloqSwab, will be dissolved in preservation solutions.

The investigators will allocate randomly the women to two different self sampling devices differing in having or not a preservative buffer

Self sampling device

Women are inviated with a standard invitation letter to perform cervical ThinPrep sampling at the clinic on a pre-fixed date

Cervical ThinPrep sampling

Francesca M Carozzi, PhD

Cristina Sani, Dr

Francesca M Carozzi, Phd

The aims of the present study are to assess the effects of a hrHPV self-sampling test as strategies to reach non-attending women in organized cervical screening in comparison with standard recall by letter in 8000 women; to evaluate the performance of two self sampling devices with and without a preservative buffer and to explore their acceptability among invited women and to evaluate a molecular triage approach for management of HPV positive women in self sampling collected material by HPV genotyping and DNA methylation marker panel

The study will be performed in the Tuscany Region including three organised screening programmes : Florence, Viareggio, and Carrara. In these areas, cervical screening programmes actively invite all the resident female population aged 34-64 years for HPV (Human Papilloma Virus) test as primary screening test (Florence and Viareggio), according to the new protocol for cervical cancer screening in Tuscany Region, or Pap-test every 3 years (Carrara). Women aged 34-64 years who had been invited by the screening programme in the previous round of screening and had failed to respond for at least 3 years will be eligible for mail recall.

In the 3 involved screening programs , every year about 63.000 in the age class 34-64 years are invited to participate at the screening program and about 40% of women do not responded to the invitation of the program. Out of them, 8000 eligible women consecutively selected from the lists will be randomised in two groups. The aim is to evaluate the response rate to invitation to a self obtained vaginal-cervical sample for hr-HPV infection testing in comparison to the standard written reminder letter. Randomisation will be performed centrally by the coordinating centre (ISPO) using computer generated random numbers. In the first year a random sample of 4000 eligible women from the 4 screening programs will be invited to participate in the study sending self sampling at home. In the control arm , the women will receive the usual recall with a new invitation letter with a prefixed appointment (it can be moved with a phone call) to perform HPV screening test in the local districts or clinic. In the intervention arm selected to receive self sampling at home, the investigators will allocate randomly the women to 2 different self sampling devices differing in having or not a preservative buffer.

So the group of women allocated in the intervention arm (4000) will be further randomized 1:1 for receiving S-wet or S-dry device .

Assuming that the compliance for the traditional method with an invitation letter is equal to 15% (Giorgi Rossi 2010), the present study is designed to be able to detect an absolute difference of 1.5% or greater in the attendance rate with a conventional levels of power (80%) and significance (95%, one side test) with a planned sample size of 8000 women. Assuming a sample size equal to 2000 women for each sampling devices, a significant difference equal to or greater than 4.0 percentage points more or less , considering a HPV positive rate of about 21% (Giorgi Rossi 2010) with same power and significance.

The study will be submitted , before starting, for approval to the Coordinating Center and Area Vasta Local Ethical Committees. Each women in the study groups will receive an alerting letter explaining that the local Public Screening Program would provide her with a box containing a self-sampler device completely free of charge to perform self- HPV screening test directly at home. After 1 week, each screening program involved in the study will ship by regular mail at home of the randomised women a letter of invitation to participate in the HPV screening program and a box with: self-sample sampling device, a HPV screening leaflet in use in Tuscany Region Program. Information related to the study, instructions to perform self-sampling, pre-printed labels to put on the tube, the informed consent form to sign , the questionnaire and a pre-stamped envelope to return the self-sampling kit. Questionnaires will be send with self-sampling device including items related to: date of women's latest Pap-test, questions about the self-sampling performance (pain, embarrassment, feasibility), what was mostly appreciated in the self-sampling (doing it by themselves, privacy, absence of a doctor, absence of speculum) and what they did not like regarding self-sampling (pain, the device, the instruction ). All information will be collected using 5-point ordinal scales on the general acceptability. Women that decide to participate in the study can send directly by regular mail to the local screening program the pre-stamped envelope with the self-sampling, the questionnaire and the signed informed consent (which will also include the authorization for telephone contact). In second year of study in the city of Florence the investigators will also evaluate the possibility to involve Drugstores in the distribution of self-sampling. In this case 500 randomised women will be invited by letter to perform self sampling for HPV screening test collecting the device in the drugstore. A list of drugstores which agreed to be included in the study will be available in the invitation letter. The impact on compliance and satisfaction of women will be evaluated. All HPV analysis and molecular tests will be performed in Molecular Laboratory of ISPO , the central lab for HPV screening test in Tuscany Region

DNA cobas4800 HPV test:

HPV will be evaluated with the same HPV test used in regular screening: the Cobas 4800 HPV test (Roche Diagnostics) is a qualitative in vitro test that utilizes amplification of target DNA by real-time Polymerase Chain Reaction (PCR) for the detection of 14 high-risk (HR) HPV types in a single analysis. It is a qualitative multiplex assay that provides specific genotyping information for HPV types 16 and 18, while concurrently detecting the other 12 high-risk HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) as a pooled result. ß-globin from cellular input is used as an internal control to assess specimen quality. The test is being performed on the completely automated cobas 4800 System (Roche Diagnostics), according to the manufacturer's instructions; a sample is considered positive according to the specific algorithm of the Cobas system software.

Management of enrolled women HPV negative women will receive at home the results of the screening test and they are re-invited after 5 years according to the HPV screening protocol. All women who resulted in being HPV positive will be contacted by phone to perform colposcopy and a counselling on HPV and cervical cancer risk. If the colposcopy will be positive, a biopsy will be taken, and each women will be followed according to the protocol of HPV screening program in Tuscany. If colposcopy will be negative, women will be re-invited to undergo control with HPV test within a year's time. During colposcopy also a Pap test will be taken to guide the post colposcopic follow-up according to the protocol approved in Tuscan Region. If a woman with hr-HPV did not attend, efforts were made to contact her again by phone and then also by letter.

Molecular Triage of HPV positive women

HPV Genotyping :

Specific genotyping will be performed in all hrHPV positive samples. DNA extracted will be genotyped. In all HPV positive self-collected samples the investigators will perform quantitative methylation analyses in order to obtain a quantification for the methylation status of the investigated CpGs, using DNA extracted for genotyping. The investigators will evaluate Methylation of CpG islands within promoter regions of genes and microRNAs such as CADM1 (Cell adhesion molecule 1), MAL (Myelin and lymphocyte protein), and hsa-miR-124- and methylation status of the HPV regions L1 and L2. The investigators will investigate for each type the CpGs located nearby the sequence position of HPV16 CpGs which have been highlighted as associated with an increased risk of cervical intraepithelial neoplastic (CIN2+) disease: L1 nucleotide positions 5601-5616 and 6457; L2 nucleotide position 4261.

Bisulfite modification: Genomic DNA samples will undergo bisulfite modification using the commercial EpiTect Bisulfite Kit (QIAGEN). The bisulfite-modified genomic DNA will be used immediately for pyrosequencing or stored at -80°C.

Human synthetic methylated and unmethylated DNA controls for human genes and DNA from CaSki cell line or a WHO (World Health Organization) HPV16-DNA control for viral genes will be included in each modification set to check modification efficiency.

Methylation status: Methylation status in the selected genes will be evaluated on the bisulfite modified DNA. The assays will be performed employing primers selected according to published sequences (Hesselink AT et al. Mirabello L et al, Wentzensen N et al). When not available, primers will be designed using a specific software . Links with available Gene-banks will be set up for gene sequence references. A preliminary PCR reaction will be performed in a total volume of 35 microL containing 1X KCl, 2mM MgCl2 , 200 microM dNTPs, 0.5 microM of each primer (antisense biotinylated), 1.75U Taq polymerase and 6 microL modified DNA with the proper thermocycling profile. Amplification and real-time measurement was performed in the 7500 ABI system (Applied Biosystems, Foster City, CA, USA). Bisulfite modified controls for methylated and unmethylated status of cell and viral gene respectively will be included in each run.

Genotyping and Methylation results will be correlated in terms of sensitivity and specificity to histological outcome and follow-up results in HPV positive women with and without clinically meaningful cervical disease diagnosed within a two-year follow-up period.

Role of each Unit involved in the study and timeline In the first year of the study ISPO will select and randomise women , set up the study data base and the software computer validation. The boxes and all materials for the mailing of self sampling devices will be prepared.

Each screening center will invite women, will send the box with self sampling device, receive the self sampling device from the invited women, register them in the database, send the samples to ISPO. ISPO L.R.P.O (Regional Oncological Prevention Laboratory) will perform hr-HPV testing and send the results to each screening center. Each screening center will receive the hr-HPV results from ISPO and send them to the woman. In case of HPV positive results the local screening center will contact the woman by phone for colposcopic assessment, perform colposcopy and every further follow-up visits, record the results and questionnaires data in the data base and participate in evaluation of the results.

In the second year ISPO will evaluate the feasibility to distribute the self sampling using pharmacies and invited women for this purpose performing hr-HPV test for responding women. ISPO will perform also HPV typing and methylation profiles, will records all data in the data base of the study, perform statistical analysis and evaluation of the results.

Self Collected Sampling in Non-attendees Cervical Cancer Screening: DNA Test and Molecular Triage for HPV Positive Women

The Value of HPV DNA Testing Using Self-collected Sampling in Non Attendees Cervical Cancer Screening and Molecular Triage Strategies on Self-sampled Material for HPV Positive Women.

The study provides that all HPV positive women of the active arm of the study will perform colposcopy. On the HPV positive woman samples the investigators carry out the molecular analysis to evaluate various molecular triage strategies (HPV genotyping, methylation of human genes (MAL-1, CADM1, hsa-miR-124-2) and methylation of viral genes L1 and L2). The molecular marker's results will be compared with the colposcopic results to evaluate its sensitivity, and specificity.

Effects of a hrHPV self-sampling test as strategies to reach non-attending women in organized cervical screening

Will be evaluated the performance of two collection systems in terms of collecting and storing the biological material for consecutive molecular analysis.

Istituto Toscano Tumori

Cancer Prevention and Research Institute, Italy

Biologist Director

All women who had not attended tthe cervical screening program in Sweden for at least 10 years were eligeble.

In this cohort study nested in the organized cervical screening program, all women who had not participated in the organized screening program for at least 10 years in one Swedish county were eligible.

Self-sampling HPV

Hanna I Sahlgren, md

Miriam K Elfström, phd

All women in one Swedish county who had not participated in the organized screening program for at least 10 years were sent an HPV self-sampling kit. Women who were positive for HPV were referred to a gynecological examination including colposcopy and further testing according to national guidelines.

In this cohort study nested in the organized cervical screening program, all women who had not participated in the organized screening program for at least 10 years in one Swedish county were eligible. Women were identified through the screening hub register that administrates for all invitations, referrals, and monitoring of the cervical screening program. The county screening hub invites approximately 30 000 women yearly to routine screening. Those who had opted out of the screening program, undergone hysterectomy, or changed their personal identification number (PNR) were excluded. HPV self-sampling kits with instructions and invitation letters were sent from the Department of Laboratory Medicine, Falun Hospital, in batches over 4 weeks. Lists of invitees were checked against changes in the screening hub register for individuals who moved, emigrated, died, or had taken a routine screening sample before sending a kit. Samples were received and HPV-analysis was performed.

If the self-sample HPV test was negative, the woman was returned to the screening program according to routine practice. HPV-positive women were referred without triage for further investigation to a gynecologist responsible for the clinical follow-up of high-risk women. The gynecological examination included colposcopy as well as biopsies and a liquid based cytology (LBC) sample (analyzed for cytology and HPV), which are routine examinations in clinical practice according to national and international guidelines. Colposcopies were performed within 3 months of a positive self-sample. If the colposcopic examination or the cytological/histopathological results indicated high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer, women underwent treatment by conization and/or hysterectomy according to national guidelines The Cobas® PCR Female Swab Sample Packet was used for self-sampling, as previous studies had determined that the sensitivity for HPV was high and comparable with cervical samples used in the organized screening program. The HPV analysis was performed at the Department of Laboratory Medicine, Falun Hospital using the Cobas 4800 HPV Test (Roche Molecular Systems, South Branchburg, New Jersey, USA).

Feasibility of Sending a Direct Send HPV Self-sampling Kit to Long-term Screening Non-attenders

Feasibility of Sending a Direct Send HPV Self-sampling Kit to Long-term Non-attenders in an Organized Cervical Screening Program

To evaluate the prevalence of high grade cervical lesions and cervical cancer cancer among long-term non-attenders in the organized screening program

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Agreement of hrHPV Type Between Self-collected Sample From Vaginal Fornix and Physician Collected Sample From the Cervical Surface	NCT04472377	Human Papilloma... Self Sampling Vaginal Dischar...	Self sampling k...	21 Years - 65 Years	Hygeia Touch Inc.
SMS-based Summons in Cervical Screening	NCT04061967	Cervical Cancer Uterine Cervica... Uterine Neoplas... Genital Neoplas... Genital Neoplas... Uterine Disease... Genital Disease... Neoplasms by Si... Neoplasms Uterine Cervica...	Sending of scre...	33 Years - 75 Years	Karolinska Institutet
IT-system Development for Reaching Cervix Cancer Screening Non-attenders	NCT02750124	Human Papilloma... Cervical Cancer	Cobas PCR Femal... Routine practic...	33 Years - 60 Years	Karolinska Institutet
Self Collected Sampling in Non-attendees Cervical Cancer Screening: DNA Test and Molecular Triage for HPV Positive Women	NCT03183700	Cervical Cancer	Self sampling d... Cervical ThinPr...	34 Years - 64 Years	Cancer Prevention and Research Institute, Italy
SMS-based Summons in Cervical Screening	NCT04061967	Cervical Cancer Uterine Cervica... Uterine Neoplas... Genital Neoplas... Genital Neoplas... Uterine Disease... Genital Disease... Neoplasms by Si... Neoplasms Uterine Cervica...	Sending of scre...	33 Years - 75 Years	Karolinska Institutet
Feasibility of Sending a Direct Send HPV Self-sampling Kit to Long-term Screening Non-attenders	NCT04909281	HPV Cervical Cancer	Self-sampling H...	33 Years - 70 Years	Falu Hospital

Spots Global Cancer Trial Database for self sampling