Ameliorated Pap Tests and Cervical Cancer Screening Participation

Not Applicable

Not yet recruiting

• Conditions: Cervical Cancer Screening; Cervical Cancer Screening Methods

• Registration Number: NCT06968871
• Lead Sponsor: National Taiwan University Hospital

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).

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-27
• Study First Submitted QC: 2025-05-05
• Last Update Submitted: 2025-05-05
• Study First Posted: 2025-05-13
• Last Update Posted: 2025-05-13
• Study Start: 2025-08
• Primary Completion: 2030-07
• Study Completion: 2032-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 248

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
3-year cervical cancer screening participation	3 years	Defined as attending a Pap test at any clinic before the end of the 3rd subsequent year following study entry

Secondary Outcome Measures

Name	Time	Method
1-year cervical cancer screening participation	1 year	Defined as attending a Pap test at any clinic before the end of the next year following study entry
3-month recalled pain intensity on a 1-5 numeric scale and a 0-10 visual analog scale	3 months after receiving the Pap smear test	Recalled pain intensity at 3 months after the Pap smear test with evaluation by a 1-5 numeric scale and a 0-10 visual analog scale. To minimize potential propaganda for cervical cancer screening participation, the investigators choose the 3-month interval rather than 6-month or 1-year intervals for long-term pain recollection after Pap tests.
5-minute recalled pain intensity on a 1-5 numeric scale and a 0-10 visual analog scale	5 minutes after receiving the Pap smear test	Recalled pain intensity at 5 minutes after the Pap smear test with evaluation by a 1-5 numeric scale and a 0-10 visual analog scale.
Real time pain during the Pap test using a 1-5 numeric scale	Every five seconds throughout the Pap test, up to completion of Pap test	The participants will evaluate and record their pain every five seconds throughout the test with an application on a 1 to 5 numeric scale. The average pain, the maximal pain, and real-time pain at the beginning, first quarter, second quarter, third quarter, and the end of the regular course are compared between the two groups. The investigators will compare the average pain of each group's first and second half of the course's course. For participants receiving the modified Pap test, the investigators further compare the average pain, the maximal pain, and the last recorded real-time pain of the 15-second step with that of the regular course.

Trial Locations

Locations (5)

National Taiwan University Hospital Beihu Branch; 🇨🇳 Taipei, Taiwan

National Taiwan University Hospital Yunlin Branch; 🇨🇳 Douliu, Taiwan

National Taiwan University Hospital Hsin-Chu Branch; 🇨🇳 Hsinchu, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

National Taiwan University Cancer Center; 🇨🇳 Taipei, Taiwan