Roles of cancer histology type and HPV genotype in HPV ctDNA detection at baseline in cervical cancer: Implications for tumor burden assessment.

Introduction: Human papillomavirus circulating tumor DNA (HPV ctDNA) is a promising biomarker for monitoring cervical cancer. HPV ctDNA level at baseline (before treatment) reflects tumor burden. However, reported HPV ctDNA detection rates at baseline have shown variations across studies, suggesting the existence of other potential contributing factors. This study aimed to identify additional factors that might influence HPV ctDNA detection at baseline, focusing on histology type and HPV genotypes (high-risk genotypes HPV16 and HPV18).

Methods: We retrospectively analysed blood samples at baseline prior to treatment from 92 patients diagnosed with HPV16- or HPV18-associated cervical cancer (FIGO IA2-IIIC2) between 2013 and 2020. HPV ctDNA was evaluated using digital droplet PCR (ddPCR).

Results: HPV ctDNA was detected at baseline in 41.3% of cases. Locally advanced cervical cancers had a higher (p = 0.028) detection rate at baseline than early stage cervical cancers. HPV ctDNA positivity was significantly (p = 0.048) higher for HPV18 (60%) than for HPV16 (34.3%). Adenocarcinoma/adenosquamous carcinoma had a higher HPV ctDNA detection rate at baseline (54.2%) than squamous cell carcinoma (36.8%), but not significantly (p = 0.212) higher.

Conclusion: This study found the impact of histology and HPV genotype on HPV ctDNA at baseline in cervical cancer. HPV18 and adenocarcinoma were associated with a higher baseline HPV ctDNA detection rate. These results suggest the need for different HPV ctDNA approaches for analyzing tumor burden. This finding may also serve as a useful reference for post-treatment surveillance studies.