Methylated ZNF582 as a triage marker for occult cervical cancer and advanced cervical intraepithelial neoplasia.

Aim: To explore the appropriate triage methods for women infected with high-risk human papillomavirus (hrHPV). Materials & methods: A total of 424 out of 872 hrHPV-infected women were divided into cervicitis (n = 123), cervical intraepithelial neoplasia grade 1 (CIN1; n = 89), CIN2 (n = 72), CIN3 (n = 87) and cervical cancer (n = 53) groups. Results: The sensitivity/specificity of ZNF582m, PAX1m and liquid-based cytology (LBC) for hrHPV-infected women with transformation zone 3 CIN3+ was 83.9/93.1, 77.4/90.6 and 80.6/58.5%, respectively. The ZNF582m/PAX1m test had a higher specificity than LBC (p < 0.001) and similar sensitivity to that observed for LBC (p > 0.05). ZNF582m/PAX1m improved the positive predictive value of CIN3+ (64.7/60.0%) in low-grade LBC (negative predictive value: 91.7/88.7%). Conclusion: ZNF582m was superior to PAX1m and LBC tests in detecting CIN3+ in hrHPV-infected women.

Human papillomavirus (HPV) testing is the main method for cervical cancer screening. Although most HPV infections are transient and can be cleared by the body, persistent infection with HPV can lead to cervical cancer. In this study, 424 HPV-infected women were divided into normal, cervical intraepithelial neoplasia grade 1 (CIN1), CIN2, CIN3 and cervical cancer groups according to the grade of cervical lesion (low to high). Women with CIN3 or cervical cancer need treatment. ZNF582^m, PAX1^m and liquid-based cytology detected 83.9, 77.4 and 80.6% of women with CIN3+ and 93.1, 90.6 and 58.5% of women without CIN3+. However, the ZNF582^m test was superior to the PAX1^m and liquid-based cytology tests.

Management of patients with positive margin after conization for high-grade cervical intraepithelial lesions.

BACKGROUND AND OBJECTIVE: To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of patients with positive margin in comparison to regular follow-up, and a repeat cervical conization. MATERIALS AND METHODS: A retrospective analysis was conducted using 83 patients with pathologically confirmed high-grade cervical intraepithelial neoplasia (CIN) with a positive margin after conization. The management methods and patient prognosis were analyzed and compared. RESULTS: Thirty-five, 33, and 15 patients were treated for regular follow-up, ALA-PDT, and a repeat cervical conization, respectively. About 33.3% (5/15) patients had residual lesions of low-grade CIN and above after recognization. The clinical characteristics of patients in the three groups were similar. The residual lesion rates of patients selected for follow-up, ALA-PDT, and recognization were 34.3% (12/35), 9.1% (3/33), and 0% (0/15), respectively, at 6-month follow-up (p = 0.004). The HPV clearance rates were 31.3%, 66.7%, and 84.6%, respectively (p = 0.01). Further analysis showed that a positive margin in the inscribed margin of the cervical canal (p = 0.022) and persistent HR-HPV positive tests after initial conization (p = 0.003) significantly increased the risk of residual disease. At 2-year follow-up, the recurrence rates of lesions were 3.3% and 26.1% in the ALA-PDT and follow-up groups, respectively (p = 0.021). Notably, the recurrence rates were not significantly different between the ALA-PDT and recognization groups (3.3% vs. 6.7%) (p = 0.561). CONCLUSION: ALA-PDT is an effective treatment for patients with a positive margin after cervical conization for high-grade CIN. Compared with regular follow-up, ALA-PDT can reduce residual and recurrence rate. Moreover, there was no significant difference in the efficacy between AlA-PDT and recognization.

Pulmonary Magnetic Resonance Imaging Replaces Bedside Imaging in Diagnosing Pneumonia in Infants.

Neonatal Bronchopulmonary Bedside Photography (NBBP) evaluates the consumption of lung magnetic resonance imaging as a replacement for bedside imaging in diagnosing infant pneumonia. In premature baby respiratory support, Neonatal Bronchopulmonary (NB) is one of the most dangerous consequences of accurate diagnosis that impact health alternatives once steroids are administered. Infants may experience eating issues and vomit if their condition is bad enough; lower birth weight, younger gestational age, and extensive breathing tube damage are the most frequently established risk factors as a component of a neonatal habitat. This paper introduces the Intelligent Medical Care (IMC) for Neonatal Bronchopulmonary Bedside Photography (NBBP), which enhances various preventive efforts such as prenatal steroid therapy. Because of many prenatal and postnatal variables, growth hormone and diet nutrients influence alveolar and vascular development. For the future prevention of NB, it is more likely that a combination of different therapies working on diverse causal pathways would be beneficial. This research in NBBP-IMC technology that enhances prenatal care medicines are the most excellent and effective treatments for all these neonates throughout the decades. As a result, premature babies at risk for NB may benefit from the findings of this research, which experts anticipate can inspire further studies in the area. The purpose of this paper is to emphasize the work performed to improve respiratory outcomes for babies at risk of NB and to place this work in perspective with relevant research currently being conducted simultaneously.

Therapeutic effects of topical photodynamic therapy with 5-aminolevulinic acid on cervical high-grade squamous intraepithelial lesions.

BACKGROUND: Topical photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is a non-invasive option for treatment of Cervical Intraepithelial Neoplasia (CIN). We investigated the clinical efficacy and safety of ALA-PDT in treatment of patients with cervical high-grade squamous intraepithelial lesion (HSIL) and evaluated the factors that effect the efficacy of PDT. METHODS: A total of 99 patients (average age: 30 years (18-45 years old)) with cervical HSIL and high-risk Human Papilloma Virus (hr-HPV) infections and who had received ALA-PDT were enrolled in this retrospective study. Before ALA-PDT, cervical exfoliated cells from all patients were obtained for HPV genotyping, liquid-based cytology test (LBC) and PAX1 methylation (PAX1m) test. Then, 6 months after ALA-PDT, HPV genotyping, LBC and colposcopy-directed biopsy were conducted. During subsequent follow-up, HPV genotyping and LBC were performed, and colposcopy-directed biopsy was conducted if hr-HPV was positive and/or LBC result was abnormal. RESULTS: At 6 months after treatment, total HPV clearance and lesions complete remission (CR) rates were 64.6% (64/99) and 88.9% (88/99), while at 1-year of follow-up, they were 81.3% (65/80) and 92.5% (74/80), respectively. At 1-year follow-up, HPV clearance rate was higher, relative to 6 months after ALA-PDT (p <0.05). At 6 months after treatment, HPV clearance and CR rates in the PAX1 hypermethylation (PAX1hm) group were 36.8% and 73.7%, which were lower compared to the rates for PAX1 hypomethylation (PAX1lm) group (71.3%, 92.5%) (p <0.05). Moreover, of the 11 patients with cervical canal lesions, 3 (3/7, 42.9%) patients had cervical canal HSIL persistence and the other 4 cervical canal HSIL and all of the 4 cervical canal LSIL had complete remission. CONCLUSIONS: ALA-PDT is an effective, safe treatment approach for patients with cervical HSIL and hr-HPV infections. Patients with PAX1lm showed better therapeutic outcomes than patients with PAX1hm or cervical canal HSIL.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) and surgery for the treatment of high-grade vaginal intraepithelial neoplasia.

OBJECTIVE: To compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and local surgical excision in the treatment of high-grade vaginal intraepithelial neoplasia (VAIN). METHODS: This was a retrospective study of a single center. Patients with biopsy-proven high-grade VAIN were counseled on the option of excision or ALA-PDT. After treatment patients were followed up at 3, 6 and 12 months and every 6 months afterwards. Clinical data of two groups were analyzed. RESULTS: Sixty patients were treated with ALA-PDT and 40 patients underwent excision surgery. The clinical characteristics of patients in the two groups were similar. The mean ages of patients treated with ALA-PDT and local surgical excision were 41.93+13.08 (18-70) and 43.25+11.64 (22-61) years old, respectively. The treatment times of PDT for patients in the ALA-PDT group were 5.48±1.41 (2-8) times. At 3-6 months after treatment, the overall complete remission (CR) rate was 93.33% (56/60) in PDT group and 82.5% (33/40) in local surgical excision group. In PDT group, a 12- and 24-month follow-up, the total HPV clearance rate was 68.97% and 77.55%, respectively. At 12-month and 2-year follow-up after local surgical excision, the total HPV clearance rate was 60% and 64.52%, respectively. Further analysis showed that the clinical efficacy was comparable between the two treatments. Patients over 45 years old exhibited a lower HPV clearance rate (P<0.05) than those under 45 years old. It was also observed that persistent HPV infection is a major risk factor for persistent disease. Further comparative analyses showed no significant difference in the CR rate and treatment times between VAINII and VAINIII in ALA-PDT group. Moreover, 4 patients (11.36%) developed recurrent lesions during follow-up after ALA-PDT, whereas 3 patients (8.33%) in the local excision group developed recurrent lesions. In addition, there was no significant difference in the recurrent rate between two groups. CONCLUSIONS: ALA-PDT shows similar efficacy and less side effects compared to local surgical excision.

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.

The effect of local photodynamic therapy with 5-aminolevulinic acid in the treatment of vaginal intraepithelial lesions with high-risk HPV infection.

BACKGROUND: Recent data has shown increased rate of vaginal intraepithelial neoplasia (VAIN) in younger individuals. Traditional VAIN treatments exert adverse effects on the anatomy and functions of the vagina. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel, non-invasive targeted therapy for intraepithelial lesions. Here, we aimed to investigate the efficacy and safety of ALA-PDT in VAIN with high-risk HPV (HR-HPV) infection. METHODS: This study enrolled a total of 82 HR-HPV-positive women diagnosed with VAIN, who were receiving ALA-PDT. The effect of ALA-PDT was evaluated using HPV genotyping and Thinprep cytologic test (TCT). Besides, colposcopy directed biopsies were performed in all patients at 3-month follow-up, and in patients with positive HR-HPV and/or abnormal TCT results during the follow-up period. RESULTS: Our data showed that the HPV clearance rate was 53.7% (44/82) at 6-month follow-up and 67.1% (55/82) at 12-month follow-up. Patients with HPV16/18 combined with other HR-HPV (HPV16/18 & other HR-HPV) infection, those with a history of hysterectomy and/or older age were had significantly lower HPV clearance rate. Besides, the lesion complete remission (CR) rate was 90.2% (74/82). These results show that HPV16/18 & other HR-HPV infection was associated with significantly lower CR rates. Throughout the follow-up, 2 cases had persistent lesions (2.4%), 6 cases had partial remission (7.3%), 2 cases recurred (2.7%) but none of the patients had disease progression. CONCLUSIONS: Taken together, our data showed that ALA-PDT is an effective, safe, and alternative treatment for VAIN patients with HR-HPV infection. However, the ALA-PDT efficacy was relatively poor in patients with older age, HPV16/18 & other HR-HPV infection and/or those with a history of hysterectomy.

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.