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.