HPV16 variant lineage in response to treatment in locally advanced cervical cancer

Cervical cancer in Colombia ranks third in incidence/mortality, with HPV16 being the most frequent high-risk oncogenic type. The aim of this study was to characterize HPV16 variant lineages in the LCR, E6, and E7 regions and evaluate their association with treatment response in locally advanced cervical cancer. We conducted a retrospective cohort study using 300 formalin-fixed, paraffin-embedded tissue samples from patients with FIGO stages IB1 to IVA cervical cancer treated at National Cancer Institute of Colombia (INC-Colombia) HPV detection was performed using GP5+/GP6+ PCR, with 261 samples successfully sequenced on the Illumina MySeq platform. A custom bioinformatics pipeline was implemented for comprehensive analysis, including viral typing using Mothur Bayesian classifier with PaVE database, and deep sequencing of LCR, E6, and E7 regions using PrimalScheme-designed primers. Variant classification involved reference mapping (BWA), variant calling (FreeBayes), and functional impact analysis (SnpEff) and treatment response were evaluated using RECIST 1.1 criteria, with complete response and non-complete response, encompassing partial response, stable disease, or progression. Statistical analyses were done using Stata 11, R 4.5.0, and jamovi 2.7. Of 300 patients, 227 (75.7%) showed complete treatment response. HPV was detected in 274 cases (91.3%), with HPV16 identified in 242 (80.7%). Among 185 sequenced HPV16 samples, lineage A predominated (76.8%), followed by lineage D (23.2%), mainly D2 (11.4%). No significant differences in SNP frequency (E6, E7, LCR) between response groups were observed, indicating no clear association with treatment outcome. However, However, specific variants E7T678C, LCR 7488T-ins, and LCR 7861del showed suggestive trends (p < 0.15), possibly reflecting subtle biological effects warranting further investigation. In summary, while HPV16 lineage A was more frequent than lineage D in this cohort, our findings do not establish an association between HPV16 variant lineages or specific SNPs and treatment response, a result consistent with other studies. Our findings do not allow us to establish an association between HPV16 variant lineages and treatment response, which is consistent with other studies. Our results demonstrated distinct HPV16 lineage distribution patterns in the Colombian cohort. These findings contribute to understanding HPV16 genetic diversity in cervical cancer and its potential implications for treatment response. These results underscore the need for large scale prospective trials to definitively evaluate the role of HPV16 genetic diversity in therapeutic outcomes and encourage further research into viral variants and treatment resistance.