Current and future techniques for human papilloma virus (HPV) testing in oropharyngeal squamous cell carcinoma

Abstract

Despite a reduction in smoking and alcohol consumption, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising. This is attributed to human papilloma virus (HPV) infection and screening for HPV is now recommended in all cases of OPSCC. Despite a variety of clinically available tests and new non-invasive test strategies there is no consensus on which technique is best. This review reports on current techniques for HPV detection in OPSCC and the clinical applicability of emerging techniques. Literature searches of Medline, Embase and clinicaltrials.gov using the search terms 'head and neck neoplasms', 'squamous cell carcinoma' and 'HPV testing' were performed. 45 studies were identified and included. p16 immunohistochemistry (IHC), HPV DNA in situ hybridization (ISH) and HPV polymerase chain reaction (PCR) are the commonest tests to determine HPV status. p16 IHC and HPV DNA PCR are highly sensitive whilst HPV DNA ISH is more specific, these techniques conventionally utilize surgical biopsies. New tests using PCR to screen fine needle aspirates, saliva, brush cytology and serum for HPV are promising but have variable sensitivity and specificity. These non-invasive samples avoid the morbidity of surgical biopsies and need for tissue blocks; their clinical role in screening and surveillance remains largely untested. Further work is needed to validate these tests and define their role.

Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

“…55 HPV-RNA assessment using the E6/E7 mRNA in situ hybridization identifies transcriptionally active HPV which might be considered the gold standard for high-risk HPV detection. [64][65][66][67] Therefore, the use of p16 expression as a surrogate biomarker to OPSCC has limitations in SCCUP. 57 Immunohistochemical p16 expression as an indicator of HPV infection has gained wide popularity after the development of commercially available and low-cost antibodies.…”

Saliva testing for human papilloma virus in oropharyngeal squamous cell carcinoma: A diagnostic accuracy study

“…There is considerable debate as to the optimum test for HPV . The commonly described techniques of p16 IHC, HPV DNA ISH and PCR on tumour tissue have associated advantages and disadvantages . HPV DNA ISH is able to demonstrate HPV integration within tumour cells, but as it detects DNA and not mRNA, it also does not confirm transcriptional activity .…”

“…The commonly described techniques of p16 IHC, HPV DNA ISH and PCR on tumour tissue have associated advantages and disadvantages . HPV DNA ISH is able to demonstrate HPV integration within tumour cells, but as it detects DNA and not mRNA, it also does not confirm transcriptional activity . p16 IHC, although not 100% specific, is emerging as a prognostic marker for OPSCC in its own right .…”

An update on head and neck cancer: new entities and their histopathology, molecular background, treatment, and outcome

“…As p16 overexpression is not restricted to carcinomas with active HPV infection, one main advantage of RNA ISH is its detection of the E6 and E7 proteins which are reserved for transcriptionally active HPV infection . In contrast to DNA ISH and PCR, this eliminates the detection of passenger infections otherwise causing for false‐positive results . In addition to separating OPSCC according to HPV status, RNA ISH reliably separate HPV+ OPSCC from clear cell carcinoma of the minor salivary glands which are often located to the oropharynx, show focal keratinization, show p16 overexpression, but is unrelated to HPV infection and is consequently negative with RNA ISH (Table ; ).…”