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.