In Vivo Application Of 5-Aminolevulinic Acid In The Treatment Of Papillomavirus Infection In Women With Cervical Lesions After Detection And Genotyping Using PCR Technique

摘要

Objective: The aim was to study the HPV viral genotyping in patients with abnormal PAP smears and the use of Photodynamic Therapy (PDT) for treatment of the HPV associated cervical lesions and for HPV eradication. Methods: 478 samples were collected consecutively from patients with abnormal Pap smears who visited the Department of Obstetrics and Gynecology and HPV genotyping were performed. Oncogenic HPV types were correlated with ages of the patients. PDT was given to some of patients were analyzed with regards to the outcome. Results: Out of those 478 patients, 227 (47 %) patients were HPV positive. In 123 patients (54%) out of the 227 women, oncogenic HPV type 31/33 was identified. A total of 77 patients (33%) disclosed HPV type 16/18, 27 patients (5%) disclosed HPV type 6/11. HPV 31/33 type incidence was significantly higher in age between 26-35 years. Out of the 227 patients HPV positive, 20 cases with high-risk cervical lesions HPV infection (16/18 genotype) were treated with PDT using 20% 5-ALA in five courses. 16 patients (80%) out of these 20 cases with cervical lesions associated with HPV infection were negative after treatment. Conclusion: HPV 31/33 was the most common HPV type in patients with abnormal PAP smears. Most women with cervical lesions associated with HPV infection can be successfully treated by PDT. Introduction HPV is ubiquitous worldwide and is markedly heterogeneous, such that more than 80 different genotypes have so far been identified by nucleotide sequence similarity [29]. Infection with certain oncogenic types of human papillomavirus (HPV) is considered a prerequisite for the development of the disease [23]. According to HPV PCR results, individuals with high-risk type-specific persistent infection during follow-up have a higher risk of persistent squamous intraepithelial lesion (SIL) than those with low-risk type-specific persistent infection or non-type-specific infection [12, 20, 23]. More than 80 known HPV types are specific for epithelial cells, including those of the skin, respiratory mucosa, and genital tract, and more than 35 distinctive types infect the genital epithelium. HPV types 16 and 18 are found most frequently in cervical carcinoma specimens and HPV types 31, 33, 35, 39, 45, 51, 52, 56, and 58 may also be associated with cervical cancer or premalignant lesions [4, 21, 24, 26]. Each of the carcinogenic genital HPV types presents a different risk to patients, with the greatest burden of risk attributed to types 16 and 18. In addition, these types are interesting, as there are possible differences in the clinical properties of cervical neoplasia according to HPV type. DNA microchip systems composed of oligonucleotides [22] or robotically spotted DNAs [25] permit genome scale analysis of gene expression patterns and have been used recently in applications such as mutation detection [9,10] and genome mapping [28]. To date, more than 85 HPV types have been identified, of which at least 35 types have been found in female genital tract infections [7, 8, 32]. HPVs have been categorized into “high risk” (HPVs 16, 18, 45, and 56), “intermediate risk” (HPVs 31, 33, 35, 51, 52, and 58), and “low risk” (HPVs 6, 11, 42, 43, and 44) groups based on their relative risks for the occurrence of a high-grade cervical lesion and an invasive cancer [16]. Photodynamic therapy (PDT) is a novel treatment modality that produces local tissue necrosis with laser light after prior administration of a photosensitizing agent [11]. The optimal treatment of preinvasive cervical lesions is still not clear as all surgical techniques cause substantial cervical stroma destruction with the risk of a possible incompetent cervix. Photodynamic therapy can preserve fertility due to selective tissue destruction [3]. 5-aminolevulinic acid (5-ALA) is a precursor in synthesis of endogenous porphyrins used to sensitize tumor tissues in photodynamic therapy (PDT). It is administered topically into tumor which after the certain