Clinical trial NCT06968871: Ameliorated Pap Tests and Cervical Cancer Screening Participation
Official title: Effects of the Ameliorated Pap Test on Cervical Cancer Screening Participation: a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cervical Cancer Screening
Cervical Cancer Screening Methods
Keywords: Cancer screening participation
Cervical cancer
Multicenter
Multidisciplinary
Pain
Pap smear
Peak-end concept
Preventive medicine
Randomized controlled trial
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: National Taiwan University Hospital Hsin-Chu Branch
name: National Taiwan University Cancer Center
name: National Taiwan University Hospital Beihu Branch
name: National Taiwan University Hospital, Yun-Lin Branch
name: National Science and Technology Council
First posted: 2025-05-13
Enrollment: 248
Sex: FEMALE
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: The Pap test plays a crucial role in the early detection of cervical cancer. A pilot single-center randomized controlled trial applied the peak-end concept and added a non-painful step at the end of Pap smear screening, aimed to reduce recalled pain. However, there is still no multicenter study investigating the effect of the modified Pap test on cervical cancer screening participation in women who are never screened or under-screened (with an increased risk of invasive cervical cancer).

The present project is the first multicenter randomized controlled trial expanding the current scope of the peak-end theory into Pap tests and cervical cancer screening participation by adding a non-painful step at the end of Pap smear screening. Our multidisciplinary team (NTUH Pap Study Group) aims to provide innovative, feasible, and low-cost strategies for cervical cancer screening participation.

Detailed description: Participants: This project expects to include women just before they undergo Pap smear screening at the NTUH Healthcare System from 2025 to 2026. The investigators include eligible women aged 25 or above who have never undergone Pap tests or have not undergone Pap tests in the past 3 years. Excluded are those who have ongoing menstruation and those who are pregnant or incapable of understanding the numeric pain scales. Women who have any active cancer at study entry (defined as cancer diagnosed or treated within the previous 6 months, recurrent, regionally advanced or metastatic cancer), previous hysterectomy, pelvic or vaginal surgery, active vaginal or uterus infection, and analgesic use within 24 hours are excluded due to potential interference with pain intensity. The study protocol is under review by the NTUH Research Ethics Committee. During the recruitment process, every eligible participant is fully informed of this trial's aim, design, and content, except for the intervention details. All participants should provide written informed consent. This study is conducted according to the Declaration of Helsinki and is going to be registered at ClinicalTrials.gov.

Sample size estimation: The investigators estimate to recruit at least 248 participants (180 at the NTUH, 68 at the NTUH Hsin-Chu, Bei-Hu, Yunlin, and Cancer Center branches), 50% (124) of whom are randomized to the intervention group, to reach 90% power for the detection of an increase in 3-year cervical cancer screening participation from 30% to 50% at the 5% level of significance.

Randomization and blinding: Eligible participants are randomly assigned to either the group receiving the traditional Pap test or the modified Pap test. Computer-generated random numbers are employed for simple randomization with a 1:1 allocation ratio. All participants are kept unaware of any information about group allocation throughout the study period. The operators performing the procedure are not informed whether to intervene by the assistants until a specimen is prepared for cervical cytology. The delayed disclosure of the group allocation until this step ensures that the operators standardized the insertion and opening phases of the Pap test. Cytopathologists who analyze the specimens are blinded to the study.

The modified and traditional Pap tests: All operators experienced in techniques for performing a Pap test should attend workshops for a standard operating procedure. The operators include family physicians and gynecologists. A well-trained research assistant is also responsible for ensuring standardization of procedures to eliminate interoperator variability. During the Pap test, there is a privacy curtain separating participants from the operators. An operator separates the labia with hand and then gently inserts the saline-lubricated speculum sideways. The speculum is rotated 90 degrees and opened to achieve an optimal view of the cervix. Then an operator fixes the speculum to obtain the cell samples by brushes. The above-standardized procedures are the same between the two groups. After preparing a specimen for conventional cytology, an operator loosens the locking nut of the speculum, partially closes the blade, rotates the speculum 90 degrees back to its original insertion orientation, and then removes the speculum in the control group receiving the traditional Pap test. For the intervention group receiving the modified Pap test, instead of immediately removing the speculum just after rotating back the speculum, an operator still fixes the speculum in the vagina for 15 seconds. Participants receiving the modified Pap test do not realize what is going on during the 15-second step because they are behind the privacy curtain. Procedurally, the subsequent addition of a non-painful step after specimen collection does not affect specimen quality.

Interview, Anthropometric Indices, and Anxiety scores: The investigators review the medical records after getting informed consent. In addition to pain evaluations, this project collects information about tobacco use, alcohol consumption, socioeconomic status, marital status, parity, sexually active status, menopause, predicted pain of Pap smears, psychological stress, anxiety score, analgesic use, current medications, and medical history through standardized personal interviews. Body height and weight are measured using a standard stadiometer, and body mass index is calculated. Blood pressure is measured with an electronic sphygmomanometer while the patient is seated after resting for at least five minutes. Psychological stress is assessed using the Brief Symptom Rating Scale -5 (BSRS-5). The BSRS-5 includes items of anxiety, depression, hostility, interpersonal sensitivity, and insomnia measured by a 5-point Likert-type scale of 0-4. Normal, slight, and great mental stress is defined by the sum of BSRS-5 scores ≤ 5, 6-9, and ≥10, respectively. The anxiety score is obtained using the Generalized Anxiety Disorder 7-item (GAD-7). GAD-7 total score for the seven items ranges from 0 to 21 (0-4: minimal anxiety. 5-9: mild anxiety. 10-14: moderate anxiety. 15-21: severe anxiety). Based on a meta-analysis, some experts have recommended considering using a cut-off of 8 to optimize sensitivity without compromising specificity.

Statistical analyses: For the descriptive analyses, values are presented as either numbers (percentages) or mean ± standard deviations. For the univariate analyses, categorical data are compared by the χ2 or Fisher's exact tests. Continuous data are compared using the independent T test. To compare screening uptake between trial groups, the investigators apply an ITT principle, such that outcomes are analyzed according to trial groups assigned regardless of whether the participants comply with intervention components of each trial group. Logistic regression analyses are utilized to estimate the association of the intervention with the probability of 3-year and 1-year uptake of cervical cancer screening. The investigators use the five-region hypothesis test based on odds ratios to test the significant indistinguishability of real-time pain between the two groups for confirming the success of randomization and blinding. The effect sizes of five-minute recalled pain on a 1-5 numeric scale and a 0-10 VAS between the two groups are calculated using Glass's delta. Linear regression analyses are used to estimate the effect of the intervention on scores of 5- minute and 3-month recalled pains. Exploratory subgroup analyses using both linear and logistic regression analyses will be performed and summarized visually using forest plots. Statistical significance levels are determined by two-tailed tests (P \< 0.05). The statistical analyses are performed with SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA).

Eligibility criteria: Inclusion Criteria:

* Women aged 25 or above who have never undergone Pap tests or have not undergone Pap tests in the past 3 years.

Exclusion Criteria:

* Ongoing menstruation
* Pregnancy
* Incapability of understanding the numeric pain scales
* Any active cancer at study entry (defined as cancer diagnosed or treated within the previous 6 months, recurrent, regionally advanced or metastatic cancer)
* Previous hysterectomy, pelvic or vaginal surgery
* Active vaginal or uterus infection
* Analgesic use within 24 hours

Primary outcomes:
measure: 3-year cervical cancer screening participation
timeFrame: 3 years
Secondary outcomes:
measure: 1-year cervical cancer screening participation
timeFrame: 1 year
measure: 5-minute recalled pain intensity on a 1-5 numeric scale and a 0-10 visual analog scale
timeFrame: 5 minutes after receiving the Pap smear test
measure: 3-month recalled pain intensity on a 1-5 numeric scale and a 0-10 visual analog scale
timeFrame: 3 months after receiving the Pap smear test
measure: Real time pain during the Pap test using a 1-5 numeric scale
timeFrame: Every five seconds throughout the Pap test, up to completion of Pap test
Other outcomes:
measure: Patient-reported feedback at the end of the study
timeFrame: At the fourth follow-up year in participants who do not undergo the 3-year cervical cancer screening; or between 1 and 12 months after the latest Pap test in participants who undergo the 3-year cervical cancer screening
Locations:
city: Douliu
country: Taiwan
facility: National Taiwan University Hospital Yunlin Branch
city: Hsinchu
country: Taiwan
facility: National Taiwan University Hospital Hsin-Chu Branch
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Cancer Center
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital Beihu Branch
Study officials:
affiliation: National Taiwan University Hospital & College of Medicine
name: Chien-Hsieh Chiang, MD, MPH, PhD
role: STUDY_CHAIR
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