Title: Clinical Characteristics, HPV Involvement, and Demographic Risk Factors in Women
with Cervical Intraepithelial Neoplasia Complicated by Vaginal Intraepithelial Neoplasia
Version: 0 Date: 31 Jan 2024
Reviewer's report:
Dear authors,
The manuscript and especially the discussion must be rewritten. See my other comments below.
Another comments
pages and lines are not numbered
Keywords: cervical intraepithelial neoplasia; vaginal intraepithelial neoplasia; HPV, HCT.
Comment: Abbreviation HPV should be explained.  What is HCT?
Introduction
“It can be divided into epithelial dysplasia and carcinoma in situ. It can also be defined as
squamous intraepithelial lesions caused by human papillomavirus infection, which can be
divided into low grade and high grade intraepithelial lesions according to the differentiation
ability of squamous cells and clinical risk. “
Introduction
“The diagnosis relies on pathological examination and its preliminary screening relies on either
thinprep cytologic test (TCT) or colposcopic application of 3% acetic acid multipoint biopsy5. “
Comment: It is more appropriate to apply 5% acetic acid to squamous cell epithelium
Study population
“A total of 212 patients diagnosed with CIN from May 2019 to May 2023 were selected, of
which 50 were CIN combined with VAIN and 160 were CIN only. “
Comment: As you write in your article: “According to statistics, the incidence of VAIN is low,
only (0.2 ~ 0.3)/100,000, accounting for 0.6% ~ 1% of cervical intraepithelial neoplasia(CIN)
and 1.0% of all female intraepithelial neoplasia in the lower reproductive tract.“
You detected 50 cases of CIN combined with VAIN from May 2019 to May 2023. But
considering what you write above, you should detect about 5000 cases of CIN in the same period.
Why did you choose only 60 CIN cases for comparison? Why these 60 cases? If you had a
larger sample of CIN, the results might be completely different. This needs to be explained and
commented on.
TCT
“According to the 2001 TBS reporting system (Bethesda 3-tier system),…“
Comment: Why not 2014  Bethesda system for reporting cervical cytology?
“Atypical squamous cells-cannot exclude HIS (ASC-H); “
Comment: Replace HIS by HSIL
HPV detection
HPV detection was relied on using microfluidic automatic nucleic acid detection technology
Comment: The name of manufacturer should be given .
Table 1
What do the numbers in brackets mean? If it is %, it must be stated.
Table 2
What do the numbers in brackets mean? If it is %, it must be stated.
HPV types
HPV16 infection was the most common in both groups. In CIN combined with VAIN group,
there were 22 cases of HPV16 infection, followed by HPV18, 52, 33 and 56. In CIN group, 71
cases were infected with HPV16, followed by HPV18, 56, 33 and 52.
Comment : The number of cases and the % must be given.
Table 3
How many were patients with VAIN 1 or VAIN 2 or VAIN 3? It should be written. The number
of cases and the % must be given.
Discussion
VAIN can be diagnosed histologically and is characterized by dysplasia of the vaginal epithelium
without interstitial invasion (citation). The risk factors of VAIN and CIN were similar, but the
incidence of CIN was significantly higher than that of VAIN (citation). In recent years, with the
development of cytology, HPV detection and more attention of colposcopists to vaginal lesions,
the detection rate of VAIN has been on the rise (citation).
There are also data showing that 72. 72% of patients have VAIN7, and patients with CIN/cervical
cancer are 82 times more likely to develop VAIN than those without CIN/cervical cancer8
Comment: I do nor understand it. Why twice 72?  72% of which patients have VAIN?
In general, the higher the level of CIN, the higher the incidence of VAIN, the higher the level.
Comment: The sentence does not make sense. Correct it.
However, the grade of VAIN is related to the grade of cervical lesions and the incidence of CIN
I and III cervical cancer is higher than other grades, and the grade of VAIN is also higher.
Comment: The sentence does not make sense. Correct it.
Over 130 species have been found, of which more than 40 can infect the cervix.
Comment:  Probably you mean 130 HPV genotypes.
According to the different parts of the invaded tissue, the skin can be divided into low-risk type
(1, 2, 3, 4, 7, 10, 12, 15) and high-risk type (5, 8, 14, 17, 20, 36, 38).
Comment:  ???????
The mucosa was low-risk (6, 11, 32, 34, 40, 42, 43, 44, 53, 54) and high-risk (16, 18, 30, 31,
33, 35, 39). Low-grade VAIN is mostly caused by high-risk subtypes (16, 18, 31, 33, 35, 45,
51, 52, 56) and low-risk types (6, 11, 42, 43, 44); High-risk HPV infection, more than 50% of
cases co-infection 16 and 18 subtypes. Some studies have suggested that vaginal lesions after
hysterectomy due to high CIN are mostly highly pathological or invasive lesions, and the HPV
binding sites in some highly pathological tissues of the vagina or vulva are consistent with the
binding sites of previous cervical lesions
Comment:  It does not make sense. Citations are missing.
Data show that more than half of VAIN patients develop HPV infection with the same type of
CIN/ cervical cancer as high.
Comment:  It does not make sense. Citations are missing.
Conclusion (summary in a few sentences) is missing