Evaluation Of Efficacy And Safety Of Photodynamic Therapy In Vaginal High-grade Intraepithelial Neoplasia

Background and ObjectiveVaginal intraepithelial neoplasia is a squamous intraepithelial neoplasia of the female lower genital tract which associated with human papillomavirus infection.It has possibility to progress to vaginal cancer.According to the severity of the disease,in 2012 the College of American Pathologists(CAP)and the American Society for Colposcopy and Cervical Pathology(ASCCP)have reclassified the VAIN,including the low-grade squamous intraepithelial lesion(LSIL)and the high-grade squamous intraepithelial lesion(HSIL).Most patients with vaginal LSIL can resolve on their own,and follow-up observation is usually sufficient.Patients with vaginal HSIL have a higher risk of developing vaginal cancer than LSIL,ranging from 2%to 13%.Therefore,patients with vaginal HSIL should be actively managed to prevent their progression to invasive cancer.At present,there are many treatment methods for vaginal HSIL,including local drug treatment,laser treatment,and surgical treatment,each with its advantages and disadvantages.Medicine treatment is relatively safe,but the treatment effect is unsatisfactory and the recurrence rate is high.Laser treatment has good curative effect and lower recurrence rate,but it has higher requirements on equipment and technology.Although the clinical effect of vaginal brachytherapy and surgical resection treatment are satisfactory and the recurrence rate is low,but there are many surgical complications.They can cause many adverse events such as shortening of the vagina,stenosis,adhesions,scar formation,damage to surrounding organs,and difficulty in sexual intercourse,which seriously affects the quality of life of patients.Especially with recurrence or new VAIN after surgery and radiation treatment,existing treatment methods are difficult to meet current needs.Photodynamic therapy(Photodynamic Therapy,PDT)is a new combination of medicine and machinery that can selectively eliminate lesions without damaging surrounding normal tissues.At present,PDT has been widely used in dermatology.In recent years,it has been gradually used for the treatment of gynecological diseases,especially in the treatment of lower reproductive tract diseases related to HPV virus infection.PDT can completely preserve the normal anatomical structure and physiological functions of organs,which can not only ensure the efficacy but also improve safety and improve the quality of life of patients.At present,PDT has achieved good results in the treatment of CIN and cervical high-risk HPV persistent infection.However,there are fewer studies on the application of PDT in patients with vaginal HSIL.The purpose of this study is to compare the efficacy and safety of surgical treatment and PDT in vaginal HSIL patients,to explore the value of PDT in the treatment of vaginal HSIL patients,and to provide a basis for the formulation of vaginal HSIL patients’ treatment plans.Materials and MethodsForty seven cases were with vaginal HSIL were treated in the First Affiliated Hospital of Zhengzhou University from August 2017 to April 2019.clinical data of all patients were collected,including:age,previous medical history,HPV typing test results,cervical/vaginal cytology test results(TCT),treatment methods,outcome and prognosis.We have grouped the vaginal HSIL patients according to the treatment method:PDT treatment group and surgical resection group.The PDT group was treated with photodynamic therapy with 5-aminolevulinic acid(ALA-PDT).Apply freshly prepared 20%ALA solution to the patient’s vaginal lesion for 3-5 hours,and then directly illuminate the patient’s lesion with 635nm red light with an energy density of 80-100 J/cm2.The treatment spot should completely cover the lesion The irradiation time is 30-40 minutes.Treatment is performed every two weeks until the lesions are completely disappeared under the colposcopy.The surgical resection group was a laparoscopic or vaginal partial vaginal resection under general anesthesia in the operating room.We used SPSS 21.0 statistical software for statistical analysis and considered that P<0.05 was statistically significant.Results1 General situation of patientsA total of 47 patients with vaginal HSIL were included in this study,including 26 in the PDT group and 21 in the surgical resection group.The average age of patients in the ALA-PDT group was(42.15±12.61)years,and the surgical resection group was(46.43±11.03)years.Seven patients(26.92%)in the ALA-PDT group had CIN,and one patient(3.85%)had vulvar intraepithelial neoplasia.There were 3 patients(14.28%)with CIN lesions in the surgical resection group.Thirteen patients(50.00%)in the ALA-PDT group had a previous history of hysterectomy,and 11 patients(52.38%)in the surgical resection group.There were no significant differences in age,history of hysterectomy,and history of cervical/vulvar intraepithelial neoplasia between the two groups(P>0.05).2 HPV test results before treatmentBefore treatment,24 patients in the ALA-PDT group were tested for HPV typing,and 23 patients(95.83%)were positive for HPV typing,including 12 HPV 16 subtypes(50.00%)and 2 HPV18 subtypes(8.33%),9 other high-risk types(37.50%);1 patient had a negative HPV test(4.17%).In the surgical resection group,19 patients were tested for HPV typing before treatment,and 18 patients were positive for HPV typing(94.74%),of which 11 were HPV 16 subtypes(57.89%)and 7 were high-risk types(36.84%).;1 patient had a negative HPV test(5.26%).there was no significant difference in HPV infection rate and distribution of HPV subtypes between the ALA-PDT treatment group and the surgical resection group(P>0.05)3 treatment effectThe median follow-up was 13 months(6-24 months),and there was no significant difference in follow-up time between the two treatment groups(P>0.05).The average number of treatments in the ALA-PDT treatment group was(4.96±1.74),of which 25 patients were cured(96.15%),only 1 patient had persistent disease(3.85%),and the HPV clearance rate was 56.52%.In the surgical resection group,20 patients were cured(95.24%),1 patient had persistent lesions(4.76%),and the HPV clearance rate was 44.44%.During the follow-up,none of the 47 patients had recurrence or advanced cancer.There was no significant difference in cure rate and HPV clearance between the two groups of patients(P>0.05).4 Adverse reactionsThere were intraoperative bleeding in 21 patients with surgical resection,ranging from 20-50ml.None of the patients had complications such as injury to the bladder,urethra and rectum.One patient developed hyperthermia due to a local incision infection,one patient experienced vaginal shortening,two patients found vaginal scarring,and two young patients reported difficulty in intercourse.All of the 26 patients in the ALA-PDT treatment group,the intensity of treatment was tolerated during the treatment.After treatment,6 patients had increased vaginal secretions,and 1 patient had intermittent lower abdominal bloating.The symptoms were mild,and they resolved on their own after 3-5 days without special treatment.None of the 26 patients treated with ALA-PDT experienced severe complications such as vaginal bleeding,infection,ulcers,poor healing,scar formation,shortening and narrowing of the vagina.Conclusion1.ALA-PDT is effective in treating patients with vaginal HSIL,and it has no significant difference with curative effect.2.ALA-PDT is safer for patients with vaginal HSIL than surgical resection.