Serum, cell-free, HPV-human DNA junction detection and HPV typing for predicting and monitoring cervical cancer recurrence

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Abstract
Almost all cervical cancers are caused by human papillomaviruses (HPVs). In most cases, HPV DNA is integrated into the human genome. We found that tumor-specific, HPV-human DNA junctions are detectable in serum cell-free DNA of a fraction of cervical cancer patients at the time of initial treatment and/or at 6 months following treatment. Retrospective analysis revealed these junctions were more frequently detectable in women in whom the cancer later recurred. We also found that cervical cancers caused by HPV types outside of phylogenetic clade α9 had a higher recurrence frequency than those caused by α9 types in both our study and The Cancer Genome Atlas cervical cancer database, despite the higher prevalence ofα9 types, including HPV16, in cervical cancer. Thus, HPV-human DNA junction detection in serum cell-free DNA and HPV type determination in tumor tissue may help predict recurrence risk. Screening serum cell-free DNA for junctions may also offer an unambiguous non-invasive means to monitor absence of recurrence following treatment.
Funding Information
  • National Cancer Institute (K08 CA273527)
  • American Association of Obstetricians and Gynecologists Foundation (Research Scholar)
  • National Cancer Institute (CA240580)
  • Foundation for Women's Cancer (ME STRONG Award)
  • National Institutes of Health (CA180922)
  • Montefiore Einstein Comprehensive Cancer Center (3A3216)

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