Human papillomavirus (HPV) positivity alone is a poor biomarker for HPV-driven head and neck cancers, according to two studies published in Cancer Research. Alternative potential markers identified in the studies include viral load, viral gene expression, and the evaluation of HPV DNA in combination with certain HPV assays.

Oropharyngeal squamous cell carcinomas (OPSCCs) that are associated with HPV infection carry a more favorable prognosis than do those that are HPV-negative, as noted in one of the studies (2012;72[19]:4993-5003). However, the investigators pointed out, it remains unclear which biomarkers can reliably determine which OPSCCs are truly driven by HPV infection.

The researchers analyzed 199 OPSCC specimens for HPV DNA, viral load, RNA expression patterns typical for cervical carcinomas (CxCaRNA+), and the HPV-targeted tumor suppressor protein p16INK4a as markers for HPV infection. They found a 49% prevalence of DNA for the cancer-associated HPV type 16, but only a 16% prevalence of high viral load and only a 20% prevalence of CxCaRNA+, a marker of HPV16 carcinogenic activity.

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Further evaluation revealed that CxCaRNA+ as a single marker conferred the lowest risk of death from oropharyngeal cancer, closely followed by high viral load. A weaker inverse association was found for OPSCCs that were HPV-positive and p16INK4a -high. The authors determined that viral load or RNA pattern analysis is better suited than p16INK4a expression to identify HPV16-driven tumors in persons with OPSCC.

In the second study, which appeared in the same issue of Cancer Research (2012;72[19]:5004-5013), investigators also sought to identify the most appropriate biomarkers for clinical assessment of HPV in head and neck squamous cell carcinoma (HNSCC). HPV16 serology was determined for 488 patients, immunohistochemical detection of p16 expression in tumors was conducted in a subset of 233 cases, and polymerase chain reaction (PCR)-based methods were used to assess the presence of HPV16 DNA in a subset of 179 cases.

Seropositivity for the HPV oncoproteins E6 and E7 was significantly associated with enhanced all-cause survival in oropharyngeal disease. Neither the presence of HPV16 DNA nor p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease, but the combination of HPV-positive DNA and E6 or E7 serology was. However, E6/E7-seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival.

Patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease, but patients who were p16-positive and E6/E7-seronegative had significantly increased risk of all causes of death.

The researchers concluded that a stronger association of HPV presence with prognosis as assessed by all-cause survival is observed when HPV-associated HNSCC is defined using tumor status (HPV DNA status or p16) and HPV E6/E7 serology in combination rather than using tumor HPV status alone.