4.3 | Interpretation
Although previous studies have revealed higher regression rates and
lower progression to CIN2+ of histologic LSIL
(CIN1),2-7 the results varied due to different study
populations, inclusion criteria, ages, hrHPV testing methods and
results, and cytological results at baseline and follow-up intervals. A
cohort study from India with 177 CIN1 women who were
HPV positive but had no baseline
cytological results yielded findings of a 15.3%
progression rate of CIN2+ within
2 years.28 In a study of 1031 histological LSIL (CIN1)
women without HPV infection status and cytological results at baseline
after 2 years of follow-up, the progression rate of CIN2+ was
6.9%.29 In this study, the 2-year risk of CIN2+ was
7.2%, which was basically consistent with previously reported
results.28, 29 The risk of progression to CIN3+ among
women with CIN1 was linked to prior cytology in the 2012 ASCCP
guidelines9 and HPV infection
status.30 A Chinese cohort study of 124 women with
histological LSIL (CIN1) found a significant difference in the
progression rate of CIN2+ within 6 years between hrHPV-positive and
hrHPV-negative women (12.7% vs. 0.0%).30 Considering
that women with histologic LSIL
(CIN1) preceded by HPV-positive or mildly abnormal cytology are
characterized by low progression rates to CIN3+ and high regression
rates within 2 years,2-7 a consecutive visit for at
least 2 years was recommended in the 2012 ASCCP
guidelines.9 In this study, the 2-year CIR of CIN3+ in
this study was 2.9%, similar to the 2.3–2.8% in the KPNC
study.12, 27
DNA-based HPV16/18 positivity has been reported to predict progression
in women with histologic LSIL (CIN1)
preceded by mildly abnormal cytology.5, 17 In the
ASC-US/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS) of
574 women patients with histologic LSIL (CIN1) preceded by DNA-based
HPV-positive/mildly abnormal cytology, the 2-year risk of CIN3 for women
positive for HPV16, HPV18, or other carcinogenic HPV genotypes was
22.1%, 17.7%, and 6.1%, respectively.5 In a 2-year
follow-up study of 273 patients with histologic LSIL (CIN1)
preceded DNA-based
HPV-positive/normal or mildly abnormal cytology, the 2-year cumulative
progression rate in the HPV16/18-positive group was significantly higher
than that in the HPV16/18-negative group (34.0% vs. 13.0%, P< 0.001).17
HPV 16, 18 and 45, which are more likely to be integrated into the human
genome than other HPV types, account for approximately 76% of invasive
cervical cancers worldwide.15, 31 In addition, the
mRNA-based AHPV test has been found to be more specific than DNA-based
HPV tests in detecting high-grade disease, although it is similarly
sensitive.18-20 The immediate risk of CIN3+ in women
with AHPV-GT-positive ASC-US cytology was significantly higher than that
in other hrHPV-positive women (10.4% vs. 2.7%, P <
0.001) as reported in our previous study.23 In a
follow-up study of 318 women with AHPV-positive/cytology-negative
results, the 18-month CIR of CIN2+ in the AHPV-GT-positive group was
significantly higher than that in the other hrHPV-positive women group
(11.5% vs. 3.6%, P < 0.001).22 In
this study, the 2-year CIRs of CIN2+ and CIN3+ were both significantly
higher in AHPV-GT-positive women at baseline than in AHPV-GT-negative
women (19.0% vs. 4.8%, P < 0.001; 8.6% vs. 1.7%,P = 0.014, respectively). Therefore, the AHPV-GT test was shown
to be an effective triaging method for women with histologic LSIL (CIN1)
preceded by AHPV-positive/normal or mildly abnormal cytology.
Few age-stratified data on the accuracy of HPV genotyping status for
triaging women with histologic
LSIL (CIN1) have supported any definitive conclusion,
and no algorithm has been
reported for triaging such women using AHPV-GT genotyping combined with
age stratification. In this study, the 2-year CIR of CIN3+ in the
25-year -or-older & AHPV-GT-negative subgroup was
1.5%, which was similar to the
0.53–1.74% and 2.3–2.8% for 1-year and 5-year CIN3+ risk,
respectively, in women with histologic LSIL (CIN1) preceded by
HPV-positive/normal or mildly abnormal cytology in the KPNC
study,12, 27 so the recommended management is 1-year
follow-up according the 2019
ASCCP guidelines.11, 27 In addition, the 2019 ASCCP
guidelines also stated that treatment was an acceptable option based on
patient preferences after shared decision-making.11Considering that the 2-year CIR of CIN3+ was up to 10.9% in the
25-year-or-older & AHPV-GT-positive subgroup, which was 7.3 times
(10.9% vs. 1.5%, P = 0.002) that of the 25-year-or-older &
AHPV-GT-negative subgroup, 1-year follow-up is a rational recommended
management for those women, and treatment (either ablative or excisional
methods) may be a better option if good surveillance is not assured. In
the 21–24-year-old group, the 2-year CIR of CIN3+ in the
AHPV-GT-negative subgroup was 0.0%, which was lower than the CIN3+ risk
value at the 1-year follow-up recommended by the 2019 ASCCP
guidelines.11, 27 Therefore, the intervals recommended
for follow-up can be extended to 2 years for the 21–24-year
& AHPV-GT-negative subgroup. The
algorithm’s recommended management of AHPV-GT testing combined with age
stratification in triaging women with histologic LSIL (CIN1) preceded by
AHPV-positive/normal or mildly abnormal cytology is shown in Figure 2.