HIFU vs Observation for LSIL of Cervix: A Randomized Controlled Trial (HIFU Colpo)

High-Intensity Focused Ultrasound (HIFU) Versus Observation for Low-Grade Squamous Intraepithelial Lesions of Cervix: A Randomized Controlled Trial

The majority of low-grade pre-invasive lesions of cervix (low-grade squamous intraepithelial lesions, LSIL).will regress spontaneously over 2 years and immediate treatment may not be necessary. According to the Hong Kong College of Obstetricians and Gynaecologists (HKCOG), if a low-grade lesion is confirmed by colposcopy and biopsy, the patient can be observed and followed up with HPV testing or co-testing at 12 months, irrespective of age. This randomized controlled study is to determine whether high-intensity focused ultrasound (HIFU) treatment of low-grade pre-invasive lesions of cervix, can cause regression of these lesions in more patients within a specific time when compared to observation as a standard management according to HKCOG Guidelines. All eligible patients will be randomized in a 1:1 ratio into 2 groups: high-intensity focused ultrasound (HIFU) or Observation group. Background information of the patients such as age, parity, body mass index, smoking status and the presence of chronic medical disease will be collected. All patients with cervical HR-HPV status will be tested. Patients randomized into HIFU group will receive HIFU treatment within 2 weeks after randomization. Those randomized into Observation group will have no intervention. All patients will attend follow-up at 6 and 12 months after randomization, during which cervical smear for cytology (with cytopathologists blinded to the treatment group) and HR-HPV testing will be performed. The rate of cytological LSIL regression and HR-HPV clearance rates at 6 and 12 months in both groups will be analyzed. Patients will be referred back to colposcopy clinic for repeat colposcopy if needed according to HKCOG Guidelines. At the 12-month follow-up visit, if referral to repeat colposcopy is not needed, patients will be referred back to their primary care physicians, Department of Health Family Health Service, Family Planning Association or other primary care centres for follow-up cervical smears.

Study Overview

• Status: Not yet recruiting
• Conditions: HPV Disease; Cervical Intraepithelial Neoplasia Grade I
• Intervention / Treatment: Device: HIFU treatment

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vincent YT Dr. Cheung, MBBS, MRCOG, FHKAM, FRCOG; Phone Number: +85222554265; Email: vytc@hku.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pre-menopausal women aged 18 years old or above.
2. Women had satisfactory colposcopy for abnormal cervical smear with positive HR-HPV test, with histologically confirmed diagnosis of cervix LSIL or CIN1.

Exclusion Criteria:

1. Women who are pregnant or breast feeding at the time of planned HIFU treatment.
2. Women without HR-HPV, or previously treated for CIN or cervical cancer.
3. Women not able to attend follow up.
4. Women with evidence of acute genital tract infection.
5. Women with significant autoimmune diseases, immunodeficiency diseases, severe cardiac, hepatic, renal, and coagulation dysfunctions.
6. Women not able to give consent.

Participants be considered withdrawn from study or excluded from analysis

1. Formally recruited into the study but withdraw from the study after randomization.
2. Do not attend both follow-up appointments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HIFU treatment group; high-intensity focused ultrasound (HIFU) for the management of cervical HR-HPV-related LSIL	Device: HIFU treatment; HIFU for the management of cervical HR-HPV-related LSIL
No Intervention: observation group; Observation group as a standard management according to HKCOG Guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of HIFU in reducing cervical HR-HPV related LSIL	- To determine the efficacy of HIFU in reducing cervical HR-HPV-related LSIL as evident by the reduction in the number of persistent cervical smear cytological abnormality when compared to observation as a standard management according to HKCOG Guidelines.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
efficacy of HIFU in clearing cervical HR-HPV	The efficacy of HIFU in clearing cervical HR-HPV-related HPV will be compared to observation. Both HIFU and Observation group will have HPV testing at 6 and 12 months after recruitment, and the incidence of HR-HPV in both groups will be analyzed.	12 months
Efficacy of HIFU in reducing the need for repeat colposcopy	The number of participants that required repeat colposcopy for persistent abnormal cervical smear in HIFU and Observation group will be compared.	12 months
Safety and side effects of HIFU in the treatment of cervical LSIL	The treatment time, intraoperative blood loss, intraoperative pain level using visual analog scale (VAS) pain score, and other discomfort are recorded. Patients will be called in 1 week for any postoperative side effects or complications such as discharge, bleeding, pain (including the VAS pain score) or discomfort, for which, additional telephone or clinic follow-up will be arranged if necessary. The visual analog scale pain score will range from a minimum value of 0 to a maximum value of 10, with higher scores mean worse pain level.	6 months
Patient satisfaction in using HIFU in the treatment of cervical LSIL	The level of patient satisfaction in using HIFU in the treatment of cervical LSIL level will be evaluated using visual analog scale (VAS) score, immediately after, and 1 month after HIFU treatment. The visual analog scale patient satisfaction score will range from a minimum value of 0 to a maximum value of 5, with higher scores mean higher satisfaction.	1 months

Collaborators and Investigators

• Sponsor: Queen Mary Hospital, Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: January 15, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cervical HR-HPV-related low-grade squamous intraepithelial lesion
• Other Study ID Numbers: UW25-292

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: not yet decided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No