Episomal HPV16 responsible for aggressive and deadly metastatic anal squamous cell carcinoma evidenced in peripheral blood

Hélène Péré,Laurent Bélec,Nicolas Robillard,Sonia Lameiras,Juliette Pavie,Marie-Laure Lucas,Alain Nicolas,Simon Pernot,Julien Puech,Raphael Vernet,Bastien Rance,Cécile Badoual,Maxime Wack,David Veyer,Laurence Weiss

doi:10.1038/s41598-021-84110-2

Abstract

Archival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral HPV16–positive metastasis were retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Full length nucleotide sequences of the same HPV16 were identified from the initial and second anal biopsy samples, from plasma sample and from vertebral metastasis biopsy. Remarkably, HPV was episomal in each sample. The HPV genome sequence was closest to the HPV16 Qv18158E variant subtype (A1 lineage) exhibiting base substitutions and deletions in 7 and 2 HPV loci, respectively. In conclusion, the powerful Capt-HPV followed by NGS allows evidencing the detailed cartography of tumoral and circulating HPV DNA, giving rise to a unique and unexpected episomal virus molecular status in a context of aggressive carcinoma, underlying the importance of HPV status and its association with clinical features for further prospective studies.

Highlights

Archival tissue samples collected longitudinally from a patient who died from HPV16-induced highgrade anal intraepithelial squamous cell carcinoma with vertebral HPV16–positive metastasis were retrospectively analyzed by the Capture-human papillomavirus (HPV) method (Capt-HPV) followed by Next-Generation Sequencing (NGS)
18 months after the initial diagnosis and resection of an HPV16-induced high-grade anal intraepithelial neoplasm (HGAIN), the patient hospitalized at Hôpital Européen Georges Pompidou (HEGP), Paris, presented vertebral HPV16–positive metastasis, associated with a paravertebral collection
The virus clearly appeared episomal in each sample, without any chimeric HPV-human genome reads potentially resulting from HPV integration in the human genome

Summary

Introduction

Archival tissue samples collected longitudinally from a patient who died from HPV16-induced highgrade anal intraepithelial squamous cell carcinoma with vertebral HPV16–positive metastasis were retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Abbreviations ASCC Anal squamous cell carcinoma Capt-HPV Capture-HPV method ctDNA Circulating tumor DNA DCF Docetaxel, cisplatin, and 5FU ECOG Eastern Cooperative Oncology Group GRCh Genome reference consortium human HEGP Hôpital Européen Georges Pompidou HGAIN High-grade anal intraepithelial neoplasm HPV Human papillomavirus MSM Men who have sex with men Scientific Reports | (2021) 11:4633. He received supportive care for 4 additional months and died 12 months after the first round of chemotherapy Witnessing this very aggressive and unexpected clinical presentation prompted us to evaluate the molecular status of the HPV16 detected in the collected samples from different origins using Capt-HPV and NGS, including the initial anal biopsy that

Methods

Results

Conclusion