Methods
The patients with biopsy-proven VaIN were recruited in the study from
April 2016 to April 2021, and followed-up until October 2021 in the
gynecological out-patient department at Tongji Hospital of Tongji
Medical College of Huazhong University of Science and Technology in
China. The patients were eligible for inclusion if the following
criteria were fulfilled: more than two pathologists diagnosed the biopsy
of the vagina as VaIN; and the patients accepted MTLA procedures and
were compliant with regular follow-up. The exclusion criteria were as
follows: 1. patients suspicious of malignant tumors of the lower
anogenital tract; 2. patients suffering unhealing malignant tumors of
other systems; 3. patients received radical hysterectomy with
after-loading radiotherapy; 4. patients with insufficient exposure of
VaIN lesions; and 5. pregnant women. Those patients diagnosed with
LSIL(VaIN1) should suffer at least one of the following risk factors:
the cytologic test suggesting HSIL, persistent HR-HPV infection,
concomitant or previous diseases of cervical or vulvar intraepithelial
neoplasia (VIN), multifocal lesions, large areas of lesions,
immunosuppression and so on. Immunosuppression was defined as suffering
the situations of autoimmune diseases, history of chemotherapy and/or
radiotherapy for cancers, using immunosuppressing drugs after organ
transplants and so on. Suitable subjects were enrolled in the study with
written informed content. This study was approved by the Institutional
Review Board at Tongji Hospital (TJ-IRB20210134) and registered at
ClinicalTrials.gov (NCT05170620).
All subjects were tested for cytology mostly with Thin-prep (Hologic
Inc, USA) and tested HPV-DNA mostly with Cervista (Hologic Inc, USA) or
Cobas 4800 (Roche Group, Switzerland). The colposcopic examinations were
completed with Leisgang colposcope (3ML, Germany). The terminology and
interpretation of colposcopy was implemented according to the 2017
criteria of the International Federation of Cervical Pathology and
Colposcopy (IFCPC). Laser ablation was performed with a
CO2 laser treatment machine (IC25, Yuhua Medical
Instruments Company in China).
The laser treatment for VaIN in the study was named multiple targeting
laser ablation (MTLA) including therapeutic laser ablation (TLA) and
strengthened laser ablation (SLA). All patients received colposcopic
examinations before initial treatment by the same gynecologist with more
than ten years’ experience to locate the lesions. The procedure of laser
ablation required targeting at the lesions in continuous mode, energy
10~20W, vaporizing 1~2mm deep and
outside 3~5mm of the lesions’ margins. TLA was defined
as MTLA with the intervals of 1~6 months until
pathological regression and HR-HPV clearance. SLA was then arranged for
some patients with high-risk factors of relapse with 1~2
number of laser ablation. The intervals between MTLA were decided
according to the wound healing state. The contents of surveillance in
therapeutic phase included cytologic tests, HR-HPV tests, colposcopic
examinations and biopsies if necessary, every 3~6
months. If suspicious VaIN lesions were found by colposcopy or
pathological examinations, repeat laser ablation was preferred. But for
a few patients suspicious of invasive lesions, surgical excisions were
performed. After accomplishing the treatment, the patients were
followed-up every 6 months in 2 years, then every 3 years after three
consecutive normal results.
The primary outcome measure was the pathological cure. Pathological cure
meant no VaIN found by colposcopy and biopsy. The secondary outcome
measure was HR-HPV negative rate. Data were collected including age,
menopause status, gravidity, parity, contraceptive methods, history of
past illness, cytologic and HR-HPV tests, colposcopic examinations,
areas of VaIN lesions, pathological examinations, parameters of laser
ablation and so on.
Meta-analysis of relevant studies was also carried out through a search
of PubMed, Cochrane Library, Web of Science, Wanfang, China Science and
Technology Journal Database, China National Knowledge Infrastructure
with the key words of “laser” and “vaginal intraepithelial
neoplasia”. The last time of searching was August
24th, 2021. Researches published in English or Chinese
were included in the meta-analysis. The screening process was accessed
by two independent researchers. Researches with samples of laser
ablation for VaIN more than 15 cases from 2000 to date were included,
and efficacy and 95% confidence interval (CI) were calculated.
The data of the study were calculated and analyzed by SPSS version 27.
Univariate analysis was performed by bivariate correlation analysis, and
multivariate analysis was performed by multivariate logistic regression
analysis with two-sided P<0.05 as statistically different.
Meta-analysis was performed by Stata 15SE. Heterogeneity was assessed by
Q statistical test with P<0.1 as statistically different. According to
the heterogeneity between studies, the random effect model was used to
calculate and combine the laser ablation efficacy.