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New ultra-sensitive detection of human papillomavirus (HPV)

Researchers have explored whether a sequencing approach, called HPV-seq, could improve detection of the human papillomavirus in patients with low levels of the disease.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. It is actually a group of more than 100 types of viruses, many of which do not typically cause health problems in the majority of people. However, in some cases, these viruses can cause genital warts (HPV 6 and 11) or cancer (HPV 31, 33, 45, 52 and 58). HPV is most commonly associated with cervical cancer (HPV 16 and 18), but it can also lead to oropharyngeal cancer or cancers of the vulva, vagina, penis and anus. These cancers often take years, or even decades, to develop after a person contracts HPV. There is also no way to determine which people who have HPV will eventually develop cancer or other health problems.

As a result, HPV screening is highly important for revealing the virus and subsequently choosing the right treatment options or predicting the most likely outcomes. Unfortunately, the current methods for HPV detection are relatively inaccurate when only low levels of the disease are present. This makes early diagnosis of HPV nearly impossible.

Detecting HPV in the bloodstream

Recently, researchers at the Princess Margaret Cancer Centre explored whether a next-generation sequencing (NGS) approach could provide an accurate and highly sensitive assessment of HPV in patients with low levels of the disease. The team published their findings in Clinical Cancer Research in the hope that the discoveries would significantly improve the detection of HPV and further refine the exact treatment of the disease.

The HPV sequencing data (HPV-seq) was analysed and applied to cohorts of advanced cervical cancer and oropharyngeal cancer patients. These results were then compared to traditional methods of HPV detection, such as digital PCR (dPCR).

The main findings were as follows:

  • HPV-seq achieved reproducible detection of HPV DNA at 20-fold lower levels of HPV circulating tumour DNA (ctDNA).
  • HPV-seq and dPCR results for patients were highly correlated. HPV-seq was able to detect ctDNA at levels down to 0.03 copy/mL plasma in dPCR-negative post-treatment samples.
  • Detectable HPV ctDNA at end-of-treatment was associated with inferior progression-free survival with 100% sensitivity and 67% specificity for recurrence.
  • Accurate HPV genotyping was successful for 100% of pre-treatment samples.
  • HPV ctDNA fragment sizes were consistently shorter than non-cancer-derived cfDNA fragments, and stereotyped cfDNA fragmentomic patterns were observed across HPV genomes.

Accurate detection of HPV

Overall, these findings suggest that HPV-seq outperforms dPCR and is a more accurate method for HPV detection. Therefore, this NGS approach could be a promising new method for monitoring HPV-related cancers and could pave the way for the development of precision medicines aimed at patients with difficult to reach cancers, such as cervical and oropharyngeal cancers.

Doctor Scott Bratman, a Senior Scientist at the Princess Margaret Cancer Centre, explained how ctDNA could be used to monitor the progress of treatment for HPV-related cancers in the future:

“In five to ten years, not everyone will be treated with the same dose of radiation and chemotherapy. Instead, we will be confident enough to give an adjusted dose. Then, patients in need of further treatment can either continue with this dose or add another treatment. This means we can save many patients from unnecessary interventions and provide a better quality of life after the cancer has healed.”

Image credit: Medpage Today

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