HPV as a marker for molecular characterization in head and neck oncology: Looking for a standardization of clinical use and of detection method(s) in clinical practice

Abstract

Background A consensus about the most appropriate diagnostic method(s) for head and neck human papillomavirus (HPV)‐induced carcinogenesis is still lacking because most of the commercially available assays have been designed for the cervix. Methods This article summarizes current data and trends concerning HPV diagnostic strategies in oropharyngeal squamous cell carcinoma (OPSCC). Six main approaches are described. Results The diagnostic gold standard for HPV‐related OPSCC, focusing on E6/E7 mRNA detection, requires fresh samples. Because most frequently available samples are formalin‐fixed paraffin‐embedded (FFPE), the pros and cons of the different approaches were analyzed. Conclusions In the FFPE samples, the immunohistochemistry of p16, which is considered appropriate to assess HPV‐driven carcinogenesis in OPSCC according to the 8th American Joint Committee on Cancer TNM classification, may not be specific enough to become the diagnostic standard in the perspective of treatment deintensification. p16 may play a safer role in combination with another highly sensible assay. Other promising approaches are based on DNA detection through real‐time polymerase chain reaction and RNAscope.

Management of HPV-Related Squamous Cell Carcinoma of the Head and Neck: Pitfalls and Caveat

“…The identification of the viral protein E6 and E7 may be the best way to identify virus-related HNSCC [15], but this methodology does not take into account some important considerations. As a matter of fact, there is a subgroup of HPV-positive HNSCC that displays both viral DNA and E6/E7 proteins which is characterized by nonviral carcinogenesis.…”

“…HPV-mediated carcinogenesis is driven by a few viral oncoproteins expressed by high-risk HPV genotypes. In particular, E6 and E7 have shown to inactivate p53 and retinoblastoma protein (pRb), respectively, and to impair several metabolic pathways in the infected cells [13][14][15].…”

“…HPV-mediated carcinogenesis is driven by a few viral oncoproteins expressed by high-risk HPV genotypes. In particular, E6 and E7 have shown to inactivate p53 and retinoblastoma protein (pRb), respectively, and to impair several metabolic pathways in the infected cells [13][14][15].The dominant viral type associated with the development of HNSCC (especially oropharyngeal carcinoma) is HPV16, while HPV18, 31 and 33 are less frequently detected [16,17]. The commonly acknowledged paradigm of HPV carcinogenesis, based on studies conducted upon uterine cervical cancer, highlights the importance of HPV genome integration as a premalignant lesion [18].…”

Evaluation of the Anyplex II HPV28 Assay in the Detection of Human Papillomavirus in Archival Samples of Oropharyngeal Carcinomas

“…The E6/E7 HPV mRNA detection has been considered the reference standard for the identification of the HPV-driven cases. 29,30 However, its application on FFPE tissues remains challenging. In absence of a gold standard assay, it is not possible to establish which are the really HPV-driven cases and the clinical significance of the presence of HPV viral sequences in cancer samples.…”

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

“…Among the key prognostic markers for survival, epidermal growth factor receptor (EGFR), cyclin D1(CCND1), ERCC1, p16, human papillomavirus (HPV), and B‐cell lymphoma‐extra large (Bcl‐xL)/Bcl‐2, as well as the amplification of genes including EMS1 , FGFR1 , and CCND1 have demonstrated some evidence in clinical trials. Others are slower to advance in clinical development because of unconvincing data and few published studies; for example, acetylcholinesterase(AchE), SNPs of specific genes, glutathione S‐transferase (GST), CD44, amplification of specific genes, hypoxic markers, KLK‐6, and MDA‐7/IL‐24; although, this does not preclude them from future investigations and clinical utility.…”