KEYWORDS
Human papillomavirus, E6/E7 mRNA,
Genotyping, LSIL, CIN1
1 | INTRODUCTION
Histologic low-grade squamous intraepithelial lesions (cervical
intraepithelial neoplasia grade 1)
(LSIL [CIN1])
can be considered transient
expression of human papillomavirus (HPV)
infection.1Considering that histologic LSIL (CIN1) preceded by HPV-positive or
mildly abnormal cytology (atypical squamous cells of undetermined
significance [ASC-US] or LSIL cytology) is characterized by a low
rate of progression to CIN2 or worse (CIN2+) of only 7.3–13.1% and a
spontaneous degeneration rate of up to 60–80% within 2
years,2-7 a consecutive visit for at least 2 years was
recommended,8-10 and treatment as an acceptable option
was added in the 2019 American Society for Colposcopy and Cervical
Pathology (ASCCP) guidelines.11 However, the overall
2-year and 5-year risks of CIN2+ in these women were only 6.4% and
10.0%, respectively, in the Kaiser Permanente Northern California
(KPNC) study.12 Therefore, in addition to increasing
the likelihood of cervical insufficiency in these women, treatment also
increases the economic burden on the healthcare
system.13, 14
HPV 16, 18 and 45 were found substantially more often in the
genome-integrated state compared with other high-risk HPV
(hrHPV) types and took
substantially less time to progress to invasive cervical cancer from a
precancerous state.15DNA-based HPV16/18 positivity,
which was slightly less likely to be followed by a negative hrHPV test
within 12 months of HPV16/18 infections than non-16/18 hrHPV
infections,16 has been reported to predict progression
for women with histologic LSIL (CIN1) preceded by mildly abnormal
cytology.17 The mRNA-based hrHPV E6/E7 mRNA assay
(Aptima HPV [AHPV]) test has been found to be more specific than
DNA-based HPV tests in detecting
high-grade disease, although it is similarly
sensitive.18-21 However, no previous report has
presented a strategy for
triaging
histologic LSIL (CIN1) preceded by AHPV-positive/normal or mildly
abnormal cytology. In the 18-month follow-up study of 318
AHPV-positive/cytology-negative women, the odds ratio of CIN2+ in AHPV
16 18/45 genotype assay (AHPV-GT)-positive vs. AHPV-GT-negative women
was 3.5 (95% CI, 1.4–8.9).22 In addition, AHPV-GT
testing was reported to be a proper risk stratification method for women
with AHPV-positive ASC-US cytology in our recent
study.23 Thus, the AHPV-GT test may have prognostic
value in histologic LSIL (CIN1) preceded by AHPV-positive/normal or
mildly abnormal cytology.
In this hospital-based longitudinal study, we evaluated the usefulness
of AHPV-GT testing combined with age stratification as a triage for
patients with histologic LSIL (CIN1) preceded by AHPV-positive/normal or
mildly abnormal
cytology.