Interpretation
Current recommended primary cervical screening methods are hrHPV tests,
cervical cytology or co-testing. However, high sensitivity of hrHPV
tests may cause patients’ psychological burden, over-referral to
colposcopy examination and over-treatment for HPV infection. Cervical
cytology assessment has a lower sensitivity and requires qualified
cytopathologists. In many rural areas in China, cytopathologists are
lacked [24]. Besides, women usually need to wait for several days or
longer to be informed of their results. Since COVID-19 broke out in
2020, routine cervical screening has become a challenge for all women
and gynecologists, as both HPV test and cervical cytology examination
could not avoid specimen contact and increase the risk of COVID-19
exposure. Until today, in COVID-19 post-pandemic, the same concern still
exists. Therefore, a simple, non-invasive and immediate screening method
is warrant.
TS detection requires no cytopathologists because of the easiness of
operation and objective results. In previous studies, TS has
demonstrated a promising diagnostic efficacy. A mate-analysis reported
the pooled sensitivity, specificity and AUC of TS was 76%, 69% and
0.7859, respectively [20]. Compared with it, TS in our study had a
relatively lower sensitivity (53.1% for CIN1+, 65.7% for CIN2+ and
67.3% for CIN3+) but a higher specificity detecting CIN1+ (77.1%) and
similar specificity detecting CIN2+ (66.7%) and CIN3+ (62.7%). A
recent study demonstrated similar diagnostic value of TS applied in
patients with abnormal Pap smear results (the sensitivity and
specificity were 65% and 55%, respectively) [19].
Among 17 ASC-H patients enrolled, 2 were TS negative. One was
pathologically confirmed CIN1, the other one was CIN3. The misdiagnose
of CIN3 by TS was TZ type I and TS-examined at outpatient department.
Colposcopically-directed three biopsies (1, 6, 11 o’clock) were
obtained. Only 1 o’clock was pathologically confirmed CIN3 while the
other two reported no lesion. We inferred that the tip of the device did
not cover the lesion since the cervix was not located in the middle and
leaning to the right, leading to the 1 o’clock area not exposed
satisfactorily.
For the missed cases of CIN2+ by TS in our study, 24 of 36 cases were
with cervical TZ type II and III (Figure 2 A3-D3). No cancer was missed
by TS. We deduced the relatively low sensitivity of TS was because of
the undetectable cervical canal and endocervix. Therefore, we defined TZ
type II and III as incomplete cervical TZ type because of the unseen SCJ
to compare with TZ type I. We unexpectedly found that TS had a better
diagnostic performance in incomplete cervical TZ type. Higher
sensitivities and significantly higher specificities and NPVs were
observed in this group. This might be attributed to the systematic bias,
as the TS operator would put the tip of device as inwardly into the
cervical canal as possible when the SCJ unexposed naturally, aiming not
to miss any lesion. Currently, women with incomplete cervical TZ type
are recommended to undergo ECC which may cause discomfort for patients
as well as operating difficulty for colposcopists. Our result indicated
that TS could reduce misdiagnosis of CIN and predict no CIN occurred
effectively, thus might decrease the frequency of ECC.
A recent study about TS applied in hrHPV infected women reported TS
combined with HPV 16/18 had the highest specificity (83.6%) comparing
with TS alone or HPV 16/18 alone [18]. Our study reported similar
specificities of TS combined with hrHPV of significancy (82.8% for
CIN1+, 73.3% for CIN2+) and significantly higher PPV of CIN1+ comparing
with hrHPV alone. This demonstrated that combination of TS and hrHPV
test could reduce misdiagnosis of CIN1+ and predict CIN1+ effectively
comparing with hrHPV alone.
Post-menopausal women usually present with cervical TZ type III. To
analyze the influence of menopause on TS detection, we compare it
between non-menopausal and post-menopausal women with cervical TZ type
III. As a result, sensitivities of non-menopausal women detecting CIN1+
and CIN3+ were significantly higher comparing with post-menopausal
women. This suggested that TS was more effective in non-menopausal
women.
In current COVID-19 post-pandemic context in China, we are eager to find
an effective screening triage method to lower the rate of colposcopy. In
our study, 89.2% and 80.3% women with negative TS result in ASCUS
group and LSIL group, respectively, were pathologically confirmed ≤CIN1.
To decrease COVID-19 exposure, gynecologists could suggest these
patients to follow up with 6 months instead of further colposcopy or
biopsy.
At last, we analyze the correlation of TS between IHC staining p16 and
Ki-67, which are important auxiliary indicators in diagnosing CIN2+
[25, 26]. We found the correlation between TS and p16, TS and Ki-67
in overall participants and ASCUS group, but all the correlation
strength were not strong. Even so, the correlations proved TS was of
high quality in diagnosing CIN.