Brief Title
Randomized Controlled Trial to Study Interventions to Increase Participation in Cervical Cancer Screening Program
Official Title
Randomized Controlled Trial to Study Interventions to Increase Participation in Cervical Cancer Screening Program
Brief Summary
Women who don't participate in Swedish cytology screening program are a minority of about
10%, but constitute the majority of those who acquire cervical cancer. Over 50 000 women in
the Västra Götalandregion have abstained from participation in the program for at least 2
screening rounds (6 - 10 years, depending om age). We plan to test two promising strategies
to increase participation. In a study of two different health policies women who have
defaulted are randomised to receiving a telephone call from a midwife, receive an offer of a
self-test for HPV or being included in a control group. This is an effectiveness study that
should give an answer how participation could be increased and give the basis for a
calculation of the costs involved, before decisions can be made about implementing either
intervention.
Detailed Description
Background
Cervical cancer today is considered as a disease that to a very large extent is preventable.
In Sweden cytological screening has been ongoing since the 60:s and this has made cervical
cancer a rare disease. Several new, but costly, methods like HPV-testing and vaccination has
been claimed to further reduce cancer incidence, but this has not been scientifically proven
so far. A recent audit of the Swedish screening program (Andrae 2008) found that the foremost
risk factor for cervical cancer in the context of the program was non participation. Women
who do participate are well protected from cervical cancer.
A Swedish study evaluating different strategies to increase participation found telephone
contact with defaulters to be the superior intervention (Eaker 2004). This study was done in
a region of Sweden with lower coverage (Sparén 2007) and less emphasis on efforts to increase
participation. A study from Kalmar, Sweden, with high coverage did not find an extended yield
to requests from non-participating women to be cost effective (Oscarsson 2007). Self testing
for HPV has been advocated as an effective method and there is a kit commercially available
(Stenvall 2007). The procedure is used as a routine in Uppsala county and marketed to other
counties.
Aim To study two possible interventions to increase participation
Design Randomised controlled trials of two interventions and a control arm
Hypothesis
Intervention with a) supportive telephone contact, by a midwife, with women who do not have a
smear registered for two screening rounds will increase participation, increase uptake of
precancerous lesions (CIN2+) and is cost effective. b) selftesting for oncogenic
papillomavirus (HPV) will increase participation and is cost effective.
Method: selection of study base
Selection was done by random among women aged 29 - 63 who did not have a pap-smear registered
within the two recent screening rounds. Women who were excluded from invitation due to total
hysterectomy and women who could be identified as have immigrated into the region under the
period were excluded before randomisation. July 1 2008 there was 52362 women who fulfilled
the first criteria (before exclusions) identified through the Register for Prevention of
Cervical Cancer in West Sweden. 8800 selected women will be included and randomised to one of
three arms with the distribution 5:1:5
Methods: Intervention Arm A: 4000 randomised women fulfilling inclusion criteria receive a
letter informing them they will be contacted by a midwife by phone, to be offered an
appointment to take a smear. They can at that stage decline such contact or if they wish
return contact information (telephone number). A week later the women who have not declined
will be called by a midwife and offered an appointment for taking a smear. Abnormal smear
will be followed up with referral to a gynecologist in concordance with normal screening
routine.
Arm B: 800 women will be sent an offer of HPV-self sampling (Aprovix, Uppsala, Sweden). By
regular mail the woman can order a test kit, and return this to the laboratory after
sampling. The samples will be tested with Hybrid Capture II for high risk HPV. A negative
result will be communicated to the women. A positive result will be sent to the gynecological
clinic responsible for the work up of abnormal cytological screening smears in the area were
the woman lives. The afflicted woman will get information from the clinic and an appointment
for colposcopy and cytology. Further investigation will be conducted as clinical routine.
Reminders will be sent to women who have ordered the kit and not returned any sample. In
order to evaluate the effect of a primary reminder women who have not responded to the
primary offer within 60 days will receive a reminder.
Arm C (controls) 4000 women will be controls. No specific action will be taken within the
study outside routine in the screening program (yearly written reminder when smears are not
found in the database)
Methods: Data collection All data about cytology, colposcopy with biopsies and treatment for
CIN are registered as a routine in the West Sweden Registry for Cervical Cancer Prevention
and data will be extracted from that registry. Data about HPV-testing will be transferred to
this registry from the Aprovix laboratory in Uppsala. Man-time needed and costs for material
and analyses for the different interventions will be registered as base for health economic
assessments.
Primary outcomes: Frequency of testing (cytology in arm A and C and HPV-test in arm B).
Frequency of further assessment of abnormal tests (all arms).
Secondary outcomes: (Arm A vs arm C) Frequency of abnormal smears. Frequency of treated CIN,
(CIN1, CIN2 and CIN3, grouped as low grade (CIN1) and high grade (CIN2, CIN3, AIS and
invasive cancer). Number of invasive cancers and FIGO stadium. Cost of interventions. Cost
per CIN2+ found. The study is powered to find a 30% difference in primary outcome based on an
expected 20% participation rate in the control group with 80% power at a significance level
of 5% for both interventions (A and B compared with C). An expected rate of abnormal smears
of 7% among these women with no smear recorded 6 or more years will give a 80% power to find
a 60% relative difference in number of abnormal smears (RR=1,6) when intervention arm A is
compared with the controls in arm C.
The results from work up of abnormal tests in arm A will be considered representative for arm
B as well, given the same level of abnormality.
The cost per participant and per biopsy with CIN found will be calculated. The cost per found
and treated high grade CIN will be compared with a reference of estimated €3500 (preliminary
figure) per CIN2+ that is eradicated.
Methods:Statistical analysis All analysis will be based on intention to treat. Pearson's Chi2
and Fischers exact test will be used to compare distribution of categorical variables between
the groups. One way variances will be used to test differences of means between groups for
continuous variables. The cumulated probability for outcome vs. follow up time will be
calculated with Kaplan-Meier analysis. Multiple Cox regression will be used to determine
relative risks. 95 % confidence intervals will be used throughout and level of significance
will be calculated two sided as 5%
Study Phase
Early Phase 1
Study Type
Interventional
Primary Outcome
Frequency of testing (cytology in arm A and C and HPV-test in arm B). F
Secondary Outcome
Frequency of abnormal smears. (Arm A vs arm C)
Condition
Cervical Intraepithelial Neoplasia
Intervention
Telephone arm
Study Arms / Comparison Groups
Telephone arm
Description: A midwife tries to contact the woman by telephone and offer her an appointment for a PAP-smear
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
8800
Start Date
September 2009
Completion Date
January 2011
Primary Completion Date
February 2010
Eligibility Criteria
Inclusion Criteria:
- No record of PAP smear in the regional screening register for more than two screening
rounds (6 - 10 years depending on age).
- Evidence in the regional population register that women have been living in the west
region of Sweden during this time.
Exclusion Criteria:
- Total hysterectomy
Gender
Female
Ages
29 Years - 63 Years
Accepts Healthy Volunteers
No
Contacts
Björn Strander, MD, PhD, ,
Administrative Informations
NCT ID
NCT01029990
Organization ID
OCGbgSw0101
Responsible Party
Sponsor
Study Sponsor
Göteborg University
Collaborators
Vastra Gotaland Region
Study Sponsor
Björn Strander, MD, PhD, Principal Investigator, Göteborg University
Verification Date
August 2012