DISCUSSION
The
residual lesions in unresected tissue after cervical conization are the
source of disease recurrence. For high-grade CIN after cervical
conization, the overall risk of residual or recurrent CIN2+ was 6.6%
(95% CI 4.9-8.4) and
was
increased with positive compared with negative resection margins
(relative risk 4.8, 95% CI
3.2-7.2)6. Therefore,
conization is considered to be safe and the preferred treatment for
high-grade CIN. However, previous literature reports, the overall risk
of residual after AIS conization was between
14.1-52.8%2,
7, which was significantly higher than
that of CIN. Therefore, hysterectomy is preferred for
AIS.
Further
studies found that positive conization margin was associated with a
significant increase in the risk of residual disease. A meta-analysis of
1278 AIS patients indicates that achieving negative margins after a
surgical excision
is
associated with a significantly lower rate of residual and recurrent
disease (20.3% and 2.6%, respectively) compared with patients with
positive margins (52.8% and 19.4%,
respectively)2.
Baalbergen8 reviewed 965 AIS patients in 35 studies,
showed that the residual rate was 16.5% in negative margins versus
49.3% in positive margins. In this study, the overall rate of residual
diseases was 16.13% in 310 specimens of hysterectomy and repeated
conization. The rates of residual disease were 50.56% (45/89) for
positive margin and 2.26% (5/221) for negative margin, respectively,
with a significantly difference (p=0.000).
On
the other hand, residual invasive cancer is the greatest risk for the
safety of conization.
Retrospective
studies reported that the rate of residual invasive cancer was less than
6%2,
even
lower in the negative margin patient. In our study the rates of residual
invasive cancer were 5.26% (5/89) for positive margin and 0 % (0/221)
for negative margin, respectively.
Our
and
previously
reported
data suggest that the risk of residual lesion and residual invasive
cancer was low after
conical
resection, provided the margin was negative.
Recurrence
of the disease is the ”golden standard” for determining the safety of
cervical conization for AIS.
As
the literature reported, the recurrent rate was about 0-5% in AIS
patients underwent conization, and 0-3% in those with negative margins7-11.
Baalbergen8 reviewed 36 studies
involving
1277 AIS patients who were diagnosed by conization and underwent
conservative treatment, 64 (5%) patients
relapsed,
of whom 3% had negative margins. Hanegem et al12 performed a
retrospective study including 112 young(age ≤30 years) patients with AIS
treated conservatively, but no recurrence was found. In this study,
totally 5 patients recurred during mean 50.09 months follow-up period,
and the recurrent rates were 1.33% in patients treated by hysterectomy
and 0.65% in patients treated by cervical conization(s) alone, with no
significant difference (p=0.431).
Moreover,
no
invasive adenocarcinoma recurrence was
identified
in patients with negative conization margins. Both univariate and
multivariate analysis did not demonstrate that surgery method was
associated with recurrence. Our results suggested that the recurrent
rate was extremely low for AIS patients with negative conization margin.
Hysterectomy
eliminates
recurrence of CIN, but can not reduce the recurrence of vaginal lesions.
“Long-term
follow-up
with
a combination of co-testing and
colposcopy
with
endocervical
sampling” is a recommended strategy for AIS patients treated with
conization,
according
to the American Society for Colposcopy and Cervical Pathology (ASCCP)
guidelines13.
The
recommendation by ASCCP guidelines was supported by previous studies, in
which cytology, HPV testing, and colposcopy evaluation was regarded as
irreplaceable
in monitoring recurrence of AIS with conservative treatment14,
15. In this study, we found that both
cytology and HPV status were independent factors influencing recurrence
of
AIS.
All
recurrent
patients were diagnosed by combined cytology and HPV testing followed by
colposcopy at the
precancerous
stage, and no patient
progressed
to invasive cancer.
In summary, the rates of residual disease in specimens of hysterectomy
and repeated conization were 50.56 % for positive margin and 2.26 %
for negative margin,
among
310 cervical AIS patients undergoing conization. During mean 50.09
months follow-up period, 1 patient recurred as CIN in those treated by
conization alone and 4 recurred as VAIN in those treated by
hysterectomy, and no invasive cancer recurrence was found. Surgery
method was not an independent factor influencing residual and
recurrence. Our results suggest that conization is an effective and safe
option for patients with AIS of the cervix, provided the margin is
negative.
Declarations
section
Declaration of Conflict of Interest: None.
All
authors of this research paper have directly participated in the
planning, execution, or analysis of the study and have read and approved
the final version submitted. This
paper is new and has been seen and approved by all listed authors. These
authors contributed equally: Jingjing Liu, Yu Wang.
The
study was approved by the Human Research Ethics Committee of the Women’s
Hospital Zhejiang University School of Medicine on June 28, 2021, and
the reference number is PRO2020-656.
Acknowledgement: This research was supported by Natural Science
Foundation of Zhejiang province China
NO.LY19H160043.