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.