Abstract:

Objective To evaluate the efficacy and safety of an infrared thermal therapy device for cervical high-risk human papillomavirus （HR-HPV） infection. Methods A prospective， multicenter， randomized， non-treatment-controlled， superiority trial was conducted. Patients with nucleic acid test-confirmed cervical HR-HPV infection and normal ThinPrep Cytology Test （TCT） results were enrolled and randomly assigned in a 2∶1 ratio to the treatment group （infrared thermal therapy device， 44 ℃， 30 min per session， 10 sessions over approximately 7 weeks） or the control group （no intervention）， with follow-up through 6 months after the initial treatment. The primary endpoint was the HR-HPV clearance rate at 6 months， defined as the conversion of at least one baseline-positive HR-HPV subtype to negative. Secondary endpoints included HPV subtype clearance rates at each visit， clinical cure rate （clearance of all baseline-positive subtypes）， life satisfaction， treatment compliance， Visual Analogue Scale （VAS） pain scores， and device performance. Statistical analyses were performed on the Full Analysis Set （FAS） and Per Protocol Set （PPS）. A superiority margin of 10% was used for superiority testing： the rate difference between groups and its 95% confidence interval （CI） were calculated using the stratified Newcombe method adjusting for center effects， with superiority declared if the lower bound of the 95%CI for the rate difference exceeded 10%. Between-group comparisons were performed using the Cochran-Mantel-Haenszel （CMH） chi-square test adjusting for center effects for difference testing， and Fisher's exact test was used when expected cell frequencies were < 5 in 2 × 2 tables. The 95% CIs for rates within each group were calculated using the Clopper-Pearson exact method. Results A total of 97 patients were enrolled （65 in the treatment group， 32 in the control group）， with 96 included in the FAS （64 treatment， 32 control）. At 6 months， FAS analysis showed a viral clearance rate of 73.4% （47/64， 95%CI： 60.9% ⁃ 83.7%） in the treatment group versus 31.3% （10/32， 95%CI： 16.1% ⁃ 50.0%） in the control group， with a rate difference of 42.2% （95%CI： 18.6% ⁃ 60.1%）. The lower bound of the 95% CI for the rate difference （18.6%） exceeded the 10% superiority margin， confirming superiority （CMH χ² = 17.51， P < 0.001）. PPS results were consistent ［77.0% （47/61） vs. 32.3% （10/31）， rate difference 44.8% （95%CI： 21.9% ⁃ 62.9%）， superiority confirmed］. Secondary endpoints： the clinical cure rate at 6 months was 68.8% （44/64） in the treatment group versus 28.1% （9/32） in the control group （χ² = 14.24， P < 0.001）； the HPV52 subtype clearance rate was 80.0% （12/15） versus 12.5% （1/8）， with a statistically significant difference （Fisher's exact test， P = 0.005）； life satisfaction rates in the treatment group （95.3% ⁃ 100.0%） were higher than those in the control group （78.1% ⁃ 93.8%） at all visits， with statistically significant differences at D0， D45， and month 3 （P < 0.001， P = 0.038， and P = 0.038， respectively）， but not at months 4 and 6 （P = 0.186 and P = 0.762， respectively）. Treatment compliance was excellent， with a completion rate of 96.9% （62/64） at D45 and 95.3% （61/64） at 6 months. Mean VAS scores across treatment sessions ranged from 0.28 to 0.37， with a maximum of < 2.5， all below the mild pain threshold of 3. Device performance was rated as excellent （5 points） at all visits. Regarding safety， no device-related serious adverse events occurred； all adverse events reported in the treatment group were mild， except for one moderate SAE （acute pyelonephritis） assessed as unrelated to the device. No local complications or device-related adverse reactions occurred. Conclusions The infrared thermal therapy device significantly improves HR-HPV clearance rates in patients with cervical HR-HPV infection， with mild pain， high patient compliance， and a favorable safety profile. It may serve as an effective intervention for the clinical management of cervical HR-HPV infection.

Key words: high-risk human papillomavirus, thermotherapy, viral clearance rate, safety