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. 2025;92(3):123-132.
doi: 10.1159/000542638. Epub 2024 Nov 27.

Roles of Cancer Histology Type and HPV Genotype in HPV ctDNA Detection at Baseline in Cervical Cancer: Implications for Tumor Burden Assessment

Miseon Lee  1 , Eun Ji Lee  2 , Jun Kang  3 , Keun Ho Lee  4 , Sung Jong Lee  4 , Sook Hee Hong  5 , Hee Seung Kim  6 , Ahwon Lee  3   7
Affiliations

Roles of Cancer Histology Type and HPV Genotype in HPV ctDNA Detection at Baseline in Cervical Cancer: Implications for Tumor Burden Assessment

Miseon Lee et al. Pathobiology. 2025.

Abstract

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 analyzed 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.

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 posttreatment surveillance studies.

Keywords: Baseline; Cancer histology type; Cervical cancer; FIGO stage; Human papillomavirus circulating tumor DNA; Human papillomavirus genotype.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Fig. 1.
Fig. 1.
FIGO stage and HPV ctDNA detection at baseline. HPV ctDNA detection rate (a) and concentration (b) in early and advanced stage at baseline.
Fig. 2.
Fig. 2.
HPV genotype and HPV ctDNA detection at baseline. HPV ctDNA detection at baseline according to HPV genotype (a), for each histology type (b), and early and advanced FIGO stages (c).
Fig. 3.
Fig. 3.
Histology type and HPV ctDNA detection at baseline. HPV ctDNA detection at baseline according to histology type (a), for each HPV16 and HPV18 genotype (b), and early and advanced FIGO stages (c).
Fig. 4.
Fig. 4.
Survival analysis using Kaplan-Meier survival curves for comparing PFS between two groups: those with HPV ctDNA detection and those without HPV ctDNA detection (undetected).
See this image and copyright information in PMC

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