Author: Sysmex Inostics,sponsored content

Human papillomavirus (HPV) plays a key role in the development of oropharyngeal squamous cell carcinoma (OPSCC). Approximately 80% of all OPSCC cases in the U.S. are associated with HPV.1 In fact, the incidence of HPV-associated OPSCC in men has surpassed that of cervical cancer in women, making OPSCC the most common cancer caused by HPV in the U.S.2

As pharmaceutical companies seek to develop targeted therapeutics for HPV-associated cancers, access to robust biomarkers can prove invaluable for drug development.

cfHPV-DNA in plasma meets this need and represents an attractive biomarker for grading treatment response and recurrence surveillance. Here, we’ll discuss the growing role for cfHPV-DNA as a biomarker in developing novel therapeutics targeting HPV-associated OPSCC and how HPV-SEQ — a quantitative, ultrasensitive test for cfHPV-DNA — can be leveraged during development for such therapies.

The rise of cfHPV-DNA as a biomarker for HPV-associated OPSCC
It has long been known that HPV-associated oropharyngeal cancers shed HPV-DNA into the circulatory system. However, drug developers now have an opportunity to not only detect but also quantify cfHPV-DNA in plasma to assess the effectiveness of therapeutics during development.

“With real-time insights, you can get a very keen sense of how the tumor is responding to intervention during a clinical trial, including de-escalation clinical trials,” explained Nishant Agrawal, MD, co-director, head and neck surgical oncology at University of Chicago Medicine. “In the past, measuring responses has taken months or even years. But with cfHPV-DNA testing, you can do it on a weekly or even daily basis.”

Because cfHPV-DNA testing offers real-time insights from a simple blood draw, it has several applications throughout pharmaceutical development:

1. Determine patients’ trial eligibility
Leveraging cfHPV-DNA testing addresses the potential shortfalls of relying on tissue biopsies to characterize patients’ tumors — including the delay involved in collecting and analyzing tissue samples and the risk of yielding inconclusive results due to inadequate tissue sampling.

What’s more, cfHPV-DNA can be used to quickly assess a patient’s HPV subtype to determine their suitability for a subtype-specific therapy.

2. Gain real-time insights into treatment response
cfHPV-DNA testing allows pharmaceutical developers to avoid the limitations of head and neck cancer imaging surveillance. The complex anatomy of the head and neck is often further complicated by surgical and post-treatment changes, as well as the risk of observing pseudoprogression after treatment with immune-based therapies. Together, these pose a significant challenge, which can be reduced by complementary use of cfHPV-DNA testing.

Moreover, drug developers can quantitatively detect and track cfHPV-DNA in real time to predict efficacy of the therapeutic quickly during the duration of treatment regimen and throughout the patient’s continuum of care with a simple blood draw.

3. Detect recurrent disease early
Nearly 30% of patients with HPV-associated OPSCC experience recurrent disease, with many experiencing distant recurrence.2 HPV-SEQ detects cfHPV-DNA that is circulating in the blood, thus providing a great representation of the patient’s disease state.

In clinical studies, post-treatment detection of cfHPV-DNA accurately predicted recurrence with 100% sensitivity and 80% positive predictive value.3 “We’re seeing cfHPV-DNA predate current standard of care surveillance in identifying recurrence, by detecting molecular residual disease that is not yet evident at imaging,” explained Anna Starus, Ph.D., associate director of medical affairs and product development at Sysmex Inostics Inc. As a result, drug developers may be able to identify recurrence earlier than what is possible with the current standard of care.

HPV-SEQ provides ultrasensitive quantitative detection of cfHPV-DNA 16 and 18 throughout drug development

HPV-SEQ has high analytical and clinical sensitivity, with the ability to reliably and consistently detect as low as two copies of HPV 16 and HPV 18 DNA.4

HPV-SEQ offers:
Accurate HPV 16/18 quantification across a broad dynamic range (over five orders of magnitude)
Low quantitative variability (<30% CV above five copies)
Low level of background signal (<0.04 copies), indicating high specificity 5
Clinical sensitivity of detecting cfHPV-DNA in pretreatment baseline samples of 97.6% (95% CI, 91.5% – 99.7%) 4

The bottom line
As drug developers continue to explore treatments for HPV-associated OPSCC, access to robust biomarkers such as cfHPV-DNA is pivotal in determining eligibility, assessing treatment response and detecting recurrence early to improve patient outcomes.

“I think we’re at that point now where cfHPV-DNA for HPV-associated OPSCC clinical trials is going to continue to emerge as an increasingly important biomarker of predicting benefit from novel therapeutic strategies,” said Ari Rosenberg, MD, assistant professor of medicine at the University of Chicago Medicine.

1. Louredo, B. V. R., Prado-Ribeiro, A. C., Brandão, T. B., Epstein, J. B., Migliorati, C. A., Piña, A. R., et al.Santos-Silva, A. R. (2022, August). State-of-the-science concepts of HPV-related oropharyngeal squamous cell carcinoma: A comprehensive review. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 134(2), 190–205.

2. Lechner M, Jones OS, Breeze CE, Gilson R. Gender-neutral HPV vaccination in the UK, rising male oropharyngeal cancer rates, and lack of HPV awareness. Lancet Infect. Dis. 2019;19:131–132.

3. Sloane, H. et al. (2021) Ultra-sensitive detection and quantification of HPV DNA in the plasma of patients with oropharyngeal squamous cell carcinoma (OPSCC) enrolled in the OPTIMA 2 treatment de-escalation trial. J Clin Oncol. 39:15_suppl, 6048.


5. Rosenberg AJ, et al. BMC Cancer. 2022 Jan 3;22(1):17. doi: 10.1186/s12885-021-09146-z. PMID: 34980038; PMCID: PMC8722316.