The effect of high-risk HPV E6/E7 mRNA on the efficacy of topical photodynamic therapy with 5-aminolevulinic acid for cervical high-grade squamous intraepithelial lesions

Background: E6 and E7 high-risk human papillomavirus (HR-HPV) oncoproteins are closely associated with the initiation and progression of cervical cancer (CC) and pre-cancerous lesions. Cervical high-grade squamous intraepithelial lesions (HSIL), as pre-cancerous lesions, have a 5% chance of progressing to invasive cancer. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel non-invasive targeted therapy for intraepithelial lesions. Herein, we analyzed the effect of HR-HPV E6/E7 mRNA on ALA-PDT for cervical HSIL.

Methods: A retrospective analysis of 148 HR-HPV-positive patients diagnosed with cervical HSIL and receiving ALA-PDT was carried out. ALA-PDT was performed with 20% ALA thermosensitive gel, and irradiation at wavelength of 635 nm and density of 80-100 J/cm² for 20-30 min. The therapeutic instruments of LED and semiconductor laser were applied for cervical lesions and lesions in endocervical canal, respectively. All patients were tested for HPV E6/E7 mRNA before and after PDT, and then followed up at 3, 6, and 12 months after treatment, and every six months thereafter.

Results: At the 6-month follow up, the complete remission (CR) rate of patients' lesions was 86.5% (128/148), whereas the total HPV clearance rate was 72.3% (107/148). It was evident that positive E6/E7 mRNA before treatment had a significant effect on HPV clearance rate (66.3% VS 81.4%, P = 0.045) and CR rate (80.9% VS 94.9%, P = 0.015). The E6/E7 mRNA associated with HPV16/18 and HPV16/18 combined with other HR-HPV (HPV16/18 and other HR-HPV) affected HPV clearance (P = 0.035) and lesions CR (P = 0.039), respectively. Moreover, persistently positive E6/E7 mRNA after treatment was closely associated with poor efficacy (HPV clearance rate: P = 0.000, CR rate: P = 0.000). Throughout the follow up period, two cases recurred but none of the patients progressed.

Conclusions: This study has shown that ALA-PDT is an effective, safe, and alternative treatment for cervical HSIL, especially for the patients of childbearing age. However, its efficacy is relatively poor in patients with persistently positive E6/E7 mRNA before and after treatment, who are relatively insensitive to ALA-PDT.