Local Hyperthermia for the Treatment of Cervical Intraepithelial Neoplasias

Study Overview
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Brief Summary
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Human papillomavirus(HPV) infect epithelial cells and have the capacity to stimulate cell abnormal hyperplasia, especially by those high-risk HPV types. HPV vaccine primarily targeting HPV6/11/16/18 has been available and makes it possible to prevent cervical cancer. However, a large population was left unvaccinated, specifically for those aged ones. In clinic, patients harboring high-risk HPV is quite prevalent in China or other developing nations. Removing the virus and prevention of malignant transformation is required. Mild local Hyperthermia with a certain temperature range has been successfully used in the treatment of some diseases. It has been utilised in the treatment of some neoplasm, fungal and HPV infections. Investigators' study found that local hyperthermia at 44°C could cleared HPV in more than half of the patients with plantar warts. Investigators also note the fact that in patients with multiple lesions, the clearance of the target lesion is commonly followed by clearance of other distant lesions, a phenomenon suggesting that local hyperthermia could aid in establishing a specific immune response to eliminate HPV.So the purpose of the study is to evaluation local hyperthermia in the treatment of cervical intraepithelial neoplasias grade I and II after 3 months, with positive high-risk type HPVs, and patients with positive testing for high risk HPVs. Appropriate control arms were designed for different conditions.

Detailed Description
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Mild local Hyperthermia with a certain temperature range has been successfully used in the treatment of some diseases. It has been utilised in the treatment of some neoplasm, fungal and HPV infections. Investigators' study found that local hyperthermia at 44°C could cleared HPV in more than half of the patients with plantar warts. Investigators also note the fact that in patients with multiple lesions, the clearance of the target lesion is commonly followed by clearance of other distant lesions, a phenomenon suggesting that local hyperthermia could aid in establishing a specific immune response to eliminate HPV.So the purpose of the study is to evaluation local hyperthermia in the treatment of cervical intraepithelial neoplasias grade I and II after 3 months, with positive high-risk type HPVs, and patients with positive testing for high risk HPVs. Appropriate control arms were designed for different conditions. One control arm is local hyperthermia at 37°C for 30 mins targeted for CINⅠ, the other control arm is LEEP targeted for CINⅡ. After 3 months, to evaluate the effectivity of local hyperthermia.

Official Title
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Evaluation of Local Hyperthermia for the Treatment of Cervical Intraepithelial Neoplasias After 3 Months: a Multicenter, Single-blind, Randomized Controlled Trial

Conditions
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Cervical Intraepithelial Neoplasia, Human Papilloma Virus

Intervention / Treatment
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* Device: Local Hyperthermia at 37℃
* Device: LEEP or cold knife
* Device: Local Hyperthermia at 44℃


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 years old; generally healthy gynecological conditions, normal sexual life; high risk HPV; Cervical biopsy CIN or no cytological changes; signed informed consent Exclusion Criteria: Pregnant woman;local or systematic treatment within 3 months; Comorbidity of other severe gynecological inflammation, infection, or tumor; Comorbidity of other serious illnesses； no guarantee of timely treatment and follow-up

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Local Hyperthermia at 44℃ for HPV+/CIN-1<br>Local hyperthermia at 44℃ for 30 mins on cervical region, at days of 1,2,3 and 17, 18. HPV+ and normal cytology or HPV+/CIN-1 | Device: Local Hyperthermia at 44℃<br>* As an experimental arm, for patients with HPV+/CIN-1/CIN2 or HPV+ with normal cytology<br>|
| Sham Comparator: local hyperthermia at 37℃ for 30 mins<br>HPV+/CIN-1 | Device: Local Hyperthermia at 37℃<br>* As a control, for patients with HPV+/CIN-1 or HPV+ with normal cytology, hyperthermia at 37℃ is applied<br>|
| Active Comparator: coniztion of the cervix treatment<br>coniztion of cervix for HPV+/CIN2, including LEEP or cold knife coniztion | Device: LEEP or cold knife<br>* For patients with HPV+ / CIN-2<br>|
| Experimental: Local Hyperthermia at 44℃ for CIN2/HPV+<br>Local hyperthermia at 44℃ for 30 mins at days of 1,2,3 and 17, 18. HPV+ and CIN2. | Device: Local Hyperthermia at 44℃<br>* As an experimental arm, for patients with HPV+/CIN-1/CIN2 or HPV+ with normal cytology<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clearance rates of HPV | to evaluate the clearance rates in different treatment groups 3 month after treatment. | 3 months after the last time of treatment. | 
| scoring atypia by cytology/pathology | to evaluate atypia severity score of cervical cells 3 month after treatment. | 3 months after the last time of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| viral load measurement | to measure the HPV 16 viral load after 3 month of treatment | 3 months after the last time of treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperthermia, human papillomavirus virus, cervical intraepithelial neoplasia