Prevalence of HPV 16 and HPV 18 Lineages in Galicia, Spain

Abstract

Genetic variants of human papillomavirus types 16 and 18 (HPV16/18) could differ in their cancer risk. We studied the prevalence and association with high-grade cervical lesions of different HPV16/18 variant lineages in a case-control study including 217 cases (cervical intraepithelial neoplasia grade 2 or grade 3 or worse: CIN2 or CIN3+) and 116 controls (no CIN2 or CIN3+ in two-year follow-up). HPV lineages were determined by sequencing the long control region (LCR) and the E6 gene. Phylogenetic analysis of HPV16 confirmed that isolates clustered into previously described lineages: A (260, 87.5%), B (4, 1.3%), C (8, 2.7%), and D (25, 8.4%). Lineage D/lineage A strains were, respectively, detected in 4/82 control patients, 19/126 CIN3+ cases (OR = 3.1, 95%CI: 1.0–12.9, p = 0.04), 6/1 glandular high-grade lesions (OR = 123, 95%CI: 9.7–5713.6, p<0.0001), and 4/5 invasive lesions (OR = 16.4, 95%CI: 2.2–113.7, p = 0.002). HPV18 clustered in lineages A (32, 88.9%) and B (4, 11.1%). Lineage B/lineage A strains were respectively detected in 1/23 control patients and 2/5 CIN3+ cases (OR = 9.2, 95%CI: 0.4–565.4, p = 0.12). In conclusion, lineages A of HPV16/18 were predominant in Spain. Lineage D of HPV16 was associated with increased risk for CIN3+, glandular high-grade lesions, and invasive lesions compared with lineage A. Lineage B of HPV18 may be associated with increased risk for CIN3+ compared with lineage A, but the association was not significant. Large well-designed studies are needed before the application of HPV lineage detection in clinical settings.

Differential HPV16 variant distribution in squamous cell carcinoma, adenocarcinoma and adenosquamous cell carcinoma

“…Globally, our results confirm and expand previous reports . We communicate an increased prevalence of HPV16_D variants in ADC and ADSC compared to SCC, that had been reported in studies using samples from United States (38% of 21 ADCs compared to 3% of 37 SCCs; 41.7% of 24 ADCs compared to 2.4% of 42 SCCs; 67.5% of 40 ADCs compared to 15.9% of 69 SCCs) and from Spain (85.7% from 7 glandular pathologies compared to 28.6% from 7 SCCs). We further describe an increased prevalence of HPV16_A1‐3 variants in SCC compared to ADC or ADSC, as previously reported in two American studies (86.8% prevalence in 38 SCCs compared to 57.1% prevalence in 21 ADCs; and 75.4% prevalence in 69 SCCs compared to 25% prevalence in 40 ADCs), and in other geographically more extended works (60% of 98 SCC compared to 42% in ADC) .…”

“…A number of previous studies suggested that cervical ADCs are diagnosed in younger women than cervical SCCs . However, other large studies did not find differences in age between glandular and squamous ICCs .…”

“…Thus, oncogenic HPVs are differentially associated with the various histological presentations of ICC. This specificity is reported at the level of type and at the level of variant . Indeed, within HPV16, the HPV16_A1‐3 variants may show an increased prevalence in SCCs, while HPV16_D and to a lesser extent HPV16_A4, B and C variants might be more prevalent in ADCs …”

Human Papillomavirus 18 Genetic Variation and Cervical Cancer Risk Worldwide

“…Our LCR/E6 classification fits with other HPV18 sequences reported in the literature (10,12,(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50) and is consistent with lineage definitions based on the gold standard approach of HPV18 whole-genome sequencing (13). Although based on LCR and E6 only, our analysis included many novel variants, particularly among previously underrepresented A5 and B (sub)lineages, which would warrant sequencing the whole genomes in order to strengthen the full picture of HPV18 genetic evolution.…”

Genetic Variations of Human Papillomavirus Type 16: Implications for Cervical Carcinogenesis

“…1) (12)(13)(14)(15)(16). In particular, lineage D is reported to be preferentially associated with an increased risk of developing CIN3 or worse (CIN3＋) (17)(18)(19)(20). Lineage D is also more frequently detected in cervical adenocarcinoma than in squamous cell carcinoma (19,20), which may suggest that this variant lineage displays different biological behaviors in different histological cell types in the cervical epithelium.…”