Identification of exosomal circSLC26A4 as a liquid biopsy marker for cervical cancer.

OBJECTIVE: Circular RNA SLC26A4 (circSLC26A4) functions as an oncogene in the initiation and progression of cervical cancer (CC). However, the clinical role of plasma exosomal circSLC26A4 in CC is poorly known. This study aims to develop an accurate diagnostic method based on circulating exosomal circSLC26A4. METHODS: In this study, exosomal circSLC26A4 derived from CC cell lines (CaSki, SiHa, and HeLa) and human cervical epithelial cells (HcerEpic) was measured and compared using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Additionally, 56 volunteers, including 18 CC patients, 18 cervical high-grade squamous intraepithelial lesion (HSIL) patients, and 20 healthy volunteers, were enrolled. qRT-PCR was also performed to measure the plasma exosomal circSLC26A4 levels in all participants. RESULTS: The exosomal circSLC26A4 expression level derived from CC cells was significantly elevated compared to it derived from HcerEpic cells. Plasma exosomal circSLC26A4 levels in CC patients were significantly higher than in healthy women and HSIL patients (P < 0.05). In addition, high plasma exosomal circSLC26A4 expression was positively associated with lymph node metastasis and FIGO stage (all P < 0.05). However, no significant correlation was found between plasma exosomal circSLC26A4 expression and age, intravascular cancerous embolus, and perineural invasion (P > 0.05). CONCLUSIONS: The high exosomal circSLC26A4 expression is closely related to the occurrence of CC. Plasma exosomal circSLC26A4 can be used as a diagnostic marker for CC.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery for the treatment of vulvar squamous intraepithelial lesion.

BACKGROUND: Vulvar squamous intraepithelial lesion (SIL) is a precursor lesion of vulvar squamous cell carcinoma. The current clinical treatments for vulvar SIL cause damage to the vulvar structure, chronic pain and psychological distress. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel, non-invasive therapy for intraepithelial lesions. The objective of this study was to compare the clinical efficacy and safety of ALA-PDT with local surgical resection for vulvar SIL. METHODS: A total of 56 patients with vulvar SIL were enrolled in this retrospective study. Among them, 16 patients received local resection and 40 patients received ALA-PDT. HPV genotyping and ThinPrep cytologic test (TCT) were used to evaluate treatment efficacy. In addition, colposcopy-directed biopsy was performed in all patients at 3-month follow-up and in patients with positive high-risk human papillomavirus (HR-HPV) and/or abnormal TCT results during the follow-up. RESULTS: At 3-month follow-up and in HSIL group the complete remission (CR) rate of the ALA-PDT group and surgery group was 90.6% (29/32) and 87.5% (14/16) (P = 1.000), respectively. The HPV clearance rate of the ALA-PDT group and surgery group was 45.2% (14/31) and 43.8% (7/16) (P = 0.927), respectively. The average numbers of ALA-PDT treatments were 5.34 for HSIL patients and 4.88 for LSIL patients, respectively. The CR rate of HSIL patients and LSIL patients was 90.6% (29/32) and 75.0% (6/8) (P = 0.550), respectively. The HPV clearance rate of HSIL patients and LSIL patients was 45.2% (14/31) and 37.5% (3/8) (P = 1.000), respectively. The ALA-PDT group showed similar clinical efficacy and milder adverse effects compared with the surgical group. CONCLUSION: ALA-PDT showed similar clinical efficacy as surgery in the treatment of vulvar SIL, but with milder adverse effects and maintaining the integrity of the vulvar structure.

Effect and rational application of topical photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) for treatment of cervical intraepithelial neoplasia with vaginal intraepithelial neoplasia.

BACKGROUND: Lesions in both the cervix and vagina require an efficacious non-invasive treatment therapy such as 5-Aminolevulinic acid photodynamic therapy(5-ALA-PDT). In this study, we evaluate clinical efficacy and safety of 5-ALA PDT for cervical intraepithelial neoplasia with vaginal intraepithelial neoplasia (CIN & VAIN). METHODS: A retrospective analysis was performed on 48 patients diagnosed with CIN & VAIN and receiving 5-ALA PDT. All patients were first followed up at 3, 6 and 12 months after treatment, then every 6 months thereafter. RESULTS: Out of 1051 patients referred for CIN (4.56%), 48 were diagnosed with CIN&VAIIN. The patients had statistically significant average vaginal and cervical lesion areas of 1.22 and 0.41 cm2 respectively. 4 patients were lost during follow-up. The patients' complete remission (CR) rate was 88.64% (39/44) at 3-6 months after treatment, while the total HPV clearance rate was 46.34 and 60.98% at 3- and 12-months follow-up,respectively. HPV16/18 combined with other high-risk human papillomaviruses (hrHPV) (HPV16/18 and other hrHPV) infection exhibited a lower HPV clearance rate (P = 0.006). The treatment time in high-grade intraepithelial neoplasia (HSIL) was higher than that of low-grade intraepithelial neoplasia (LSIL). Notably, atypical vessels and endocervical canal lesions involvement significantly affected 5-ALA PDT. Moreover, 5 patients had residual lesions (11.36%) during follow-up, one patient presented recurrence (2.56%), while 4 had successful pregnancy. CONCLUSIONS: 5-ALA-PDT is a non-invasive, effective, and safe therapy for treating CIN & VAIN and can maintain the structural and functional integrity of target organs. However, its efficacy is relatively poor in patients with endocervical canal lesions involvement, atypical vessels, and HPV16/18 and other hrHPV infection.