(4)子宮頸部初期病変に対する新しい診断システムの開発と妊孕能温存治療の適応拡大に関する研究(講演要旨,<特集>第58回シンポジウム3「子宮頸部初期病変の管理と治療-標準化をめざして」)

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Objectives Screening of women for early changes in the uterine cervix is generally carried out by means of cytological examination; however, to date no procedures have been established to identify high-risk patients with lesions that may further progress among patients with dysplasia or patients positive for human papillomavirus (HPV). Recently it has become recognized that the HPV viral gene product E7 protein induces overexpression of p16^<INK4a> protein via inactivation of Rb protein; increasing attention is thus being focused on p16^<INK4a> protein as a new marker for early cervical changes. Meanwhile, cervical cancer has been increasingly seen in young women, but there is no consensus on fecundity-conserving therapy for stage Ia2 or more advanced squamous cell carcinomas and adenocarcinomas. Against this background, the present study was performed to develop a new diagnostic system for screening high-risk patients with early cervical lesions and to assess the indication for fecundity-conserving therapy for early stage cervical cancer. Materials and Methods (1) Development of a new diagnostic system to screen high-risk patients with early cervical lesions In a total of 76 patients with mild to moderate dysplasia, HPV typing as well as cytological and immunohistochemical examination using anti-p16^<INK4a> protein monoclonal antibody were performed. Using the Kaplan-Meier method, correlation between the duration of cytodiagnostic abnormalities and HPV type, and correlation between the former and p16^<INK4a> protein overexpression were investigated. To explore the potential applicability of the immunocytochemical detection of p16^<INK4a> protein overexpression to cytological examination, a study was also conducted in 25 patients with mild dysplasia, 26 patients with moderate dysplasia, 24 patients with severe dysplasia, 9 patients with intraepithelial neoplasia, 11 patients with squamous cell carcinoma, 20 patients with adenocarcinoma, and 123 patients with benign neoplasia. In addition, an attempt was made to examine usefulness of the p16^<INK4a> protein immunocytochemical approach in adjunctive diagnosis. (2) Assessments of fertility-conserving therapy for early stage cervical cancer Twenty-six patients underwent an abdominal radical trachelectomy for treatment of stage la to Ib1 cervical cancer, and they were monitored for postoperative clinical progress. In addition, of 50 patients with adenocarcinoma in situ, the clinical progress was reviewed retrospectively in 25 patients who had been followed after treatment with conization of the cervix alone. Results (1) Development of a new diagnostic system to screen high-risk patients with early cervical lesions Persistent cytodiagnostic abnormalities were more frequently noted in patients with evidence of HPV type 16, compared to those positive for other HPV types (p<0.05). Of these patients with evidence of HPV type 16, persistent cytodiagnostic abnormalities were more frequently found in those with p16^<INK4a> protein overexpression than in those with no overexpression of this marker protein (p<0.05). In the group of patients with evidence of HPV types other than type 16, the duration of cytodiagnostic abnormalities did not significantly vary depending on whether they had p16^<INK4a> protein overexpression or not. The incidence of p16^<INK4a> protein overexpression, demonstrated by immunocytochemical staining for p16^<INK4a> protein, increased with progressing dysplastic changes, i.e., mild dysplasia, 16%; moderate dysplasia, 34.7%; severe dysplasia, 62.5%; and intraepithelial carcinoma, 77.8%. Furthermore, p16^<INK4a> protein overexpression was evident in all patients with adenocarcinoma and those with squamous cell carcinoma. (2) Assessments of fertility-conserving therapy for early stage cervical cancer Of 26 patients who underwent an abdominal radical trachelectomy, 4 patients were given adjunctive therapy for postoperative lymph node metastases or parametrial involvement. Twenty-two patients were followed postoperatively, of whom 21 patients were noted to be free from recurrence over a follow-up period of 4〜37 months (mean:16.7 months), while a patient having been treated for adenocarcinoma underwent a reoperation. One patient conceived after the surgical treatment and was delivered of an infant by caesarean section at 24 weeks of pregnancy. Of 25 patients who were followed after treatment with conization of the cervix alone, the stamp was negative for dysplasia in 24 patients, and none had recurrence over a follow-up period of 9〜81 months (mean: 37.3 months). Conclusions The present data show that patients with mild to moderate dysplasias may be classified into the highrisk group, the intermediate-risk group, and the low-risk group, based on results from combined HPV typing and p16^<INK4a> protein immunohistochemical examination. In addition, p16^<INK4a> protein immunocytochemistry may be useful as a testing technique for estimating the progress of dysplasia. It has also been demonstrated that abdominal radical trachelectomy may constitute a choice of fecundity-conserving therapy for stage Ia2 and stage Ib1 squamous cell carcinomas of small tumor diameter. As treatment for adenocarcinoma in situ, patients may be followed post-operation if operated on with conization of the cervix and if the stamp remains negative for dysplasia.
社団法人日本産科婦人科学会の論文
2006-11-01

(4)子宮頸部初期病変に対する新しい診断システムの開発と妊孕能温存治療の適応拡大に関する研究(講演要旨,<特集>第58回シンポジウム3「子宮頸部初期病変の管理と治療-標準化をめざして」)

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