Introduction
Adenocarcinoma in situ (AIS) of the uterine cervix is a precursor lesion for invasive cervical adenocarcinoma1. The incidence of cervical AIS is increased over past few decades compared with high-grade cervical squamous intraepithelial neoplasia (CIN), especially among women aged 30–39 years, the average age at cervical AIS diagnosis is 36.9 years2. Unlike CIN, AIS of the cervix is recommended to hysterectomy. For women who wish to maintain fertility, cervical conization is feasible, but total hysterectomy is preferred after completing the childbearing3, 4. This type of treatment mode affects the quality of life in young patients even without reproductive requirements. The reason for concern about the safety of conservative treatment for cervical AIS is that it has long been considered as “jumping lesions with multifocal distribution-foci” of adenocarcinoma cells that are not contiguous2, even if the margin status of conization is negative, there still is a high risk of residual AIS or invasive cancer in unresected tissues. However, there is insufficient evidence to demonstrate a skip lesion in cervical AIS up to now. It has been reported that cervical conization with negative margin may be safe for cervical AIS, but more evidence is needed.
We retrospectively collected 453 patients with cervical AIS, of those, 153 underwent conization(s) alone and 300 underwent conization followed by hysterectomy. The aim of this study was to evaluate the effect and safety of the conization alone in cervical AIS patients; and to investigate the factors for recurrence or progression that may guide optimal management and follow-up.
Patients and methods
Collection of patients
All patients, who were pathologically diagnosed as cervical AIS on cervical conization specimens and underwent repeated conization, hysterectomy or followed up respectively in Women’s Hospital of Zhejiang University School of Medicine between January 2007 and May 2021, were collected using computerized databases from the Departments of Gynecologic Oncology and Pathology. Those were excluded if: i) a history of previous high-grade CIN, AIS or invasive cervical carcinoma; ii) previous surgery in cervix; iii) directly treated with hysterectomy; and iv) incomplete clinical and follow-up data. In 920 collected patients with cervical AIS, 453 eligible patients were included in this study, of those, 153 underwent conization(s) alone and 300 underwent conization followed by hysterectomy.
Medical records were reviewed, including demographic data, HPV status, cytology, colposcopy, pathologic findings, and treatment procedure and outcomes. HPV was detected by Hybrid Capture 2 (HC-II) HPV Test and ≥1 RLU/CO was defined as positive result. Cervical cytology was detected by Thinprep cytologic test (TCT) and results were classified according to the Bethesda System 2001, which classified as negative for intraepithelial lesions or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), atypical squamous cells-cannot exclude HSIL (ASC-H), squamous cell carcinoma (SCC), atypical glandular cells (AGC), adenocarcinoma in situ (AIS), and adenocarcinoma (AC). The cytology result ≥ ASC-US or AGC was defined as abnormal.
The colposcopy adopted a photoelectric integrated system, (manufactured in Leisegang, Germany), and both acetic acid and lugol’s iodine solution were used during the examination. The cervical transformation zone was classified as type I, II or III according to the International Federation for Cervical Pathology and Colposcopy in 20115.
Conization was performed by cold knife (CKC) or loop electrosurgical excision procedure (LEEP). A positive margin was defined as lesion within 1 mm from the epithelial lesion to the surgical margins. Residual disease was defined as CIN, AIS or invasive cervical cancer was pathologically found in specimens of hysterectomy or repeated conization. The indirections of hysterectomy were no child-bearing desire, older age, and/or conization with positive margin. The flowchart of patient collection was shown in Figure 1.
All pathologic diagnoses were thoroughly re-evaluated by two pathologists blindly. Recurrence was defined as the reappearance of cervical or vaginal intraepithelial neoplasia after hysterectomy or last cervical conization 3 months or later.
The study was approved by Women’s Hospital Human Research Ethics Committee.
Follow-up
All patients were followed up by cytology and HPV testing, according to the procedures, scheduled every 3 months within two years, and every 6 months for three-five years, once a year thereafter. Patients with cytology abnormal and/or HPV positive were referred to colposcopy with or without biopsy. The mean follow-up period was 50.09 months (range12~170 months) from the time of first conization to August 31, 2021.