Abstract
BackgroundThere has been a sharp rise in the incidence of human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) in many countries. Patients with HPV-positive OPSCC have a more favorable prognosis compared with HPV-negative OPSCC, leading to investigation and adoption of de-escalation treatment protocols. The baseline rate of HPV prevalence in certain populations is of epidemiologic significance. We aimed to evaluate the rate of high-risk HPV in a large cohort of Thai patients, including OPSCC, oral SCC (OSCC) and laryngeal SCC (LSCC).MethodsIn total, 504 patients with HN cancer (110 OPSCC, 260 OSCC and 134 LSCC) who had been treated in Chulalongkorn University between 2010 and 2016 formed the sample set. All histological slides were reviewed to validate the diagnosis and render the histological type as keratinizing (K), non-keratinizing (NK) or non-keratinizing with maturation (NK-M). Immunohistochemistry with p16 was performed in all cases and scored semiquantatively. Positive and equivocal cases were tested by the high-risk HPV DNA in situ hybridization (ISH). Validation with quantitative polymerase-chain reaction (qPCR) was performed in p16-positive OPSCC.ResultsThe OPSCC were represented by NK (7.3%), NK-M (16.4%) and K (76.4%) types, with an HPV incidence of 100, 22.2 and 4.7%, respectively. The average HPV prevalence in OPSCC was 14.5%. The concordance with p16/ISH was 51.6%, while concordance of the NK morphology with positive HPV ISH was 100%. ISH-qPCR concordance in p16-positive OPSCC was 72.7%. Patients with HPV-positive OPSCC had significantly more tumors with a NK histologic type, tonsillar location, earlier clinical stage, less association with smoking, and, finally, better outcome and longer survival time. In non-OPSCC, p16-positive HPV-associated cancers were found in only 1.5% of OSCC (4/260) and LSCC (2/134).ConclusionA low rate of HPV-related OPSCC was found in Thai patients. The NK morphology was an excellent predictor of high-risk HPV infection in OPSCC. For OPSCC patients, HPV-positive ones had a significantly longer survival time than HPV-negative ones. There was a lack of p16-positive HPV-related OSCC and LSCC. Morphology and p16 status had a poor predictive value for detecting HPV in OSCC and LSCC.
Highlights
There has been a sharp rise in the incidence of human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) in many countries
We aimed to evaluate the prevalence of high-risk HPV in Thai HNSCCs, including true HPV-associated (OPSCC) and potentially HPV-related cancers, based on a two-step approach combining p16 immunostaining and HPV DNA in situ hybridization (ISH)
None of them turned out to be HPV DNA-positive. In this large-scale study, we found that 14.5% of OPSCC were associated with a high-risk HPV. This low baseline rate of HPV-related OPSCC detected by the two-step approach of p16 immunohistochemistry followed by HPV DNA ISH was established in the Thai population for the first time
Summary
There has been a sharp rise in the incidence of human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) in many countries. The well-known risk factors include tobacco smoking, alcohol consumption [3] and oral betel quid use [4]. The HPV-positive oropharyngeal SCC (OPSCC) has unique clinical characteristics and tumor morphology [1, 7]. Compared to HPV-negative cancers, the HPV-positive OPSCCs tend to have a better survival outcome [8, 9]. These tumors typically arise in younger patients, especially in males with sexual-risk behaviors and no significant history of tobacco smoking, alcohol consumption or oral betel quid use [7]. HPV-associated HN cancers display non-keratinizing features, which is currently accepted as the so-called “prototypical HPV-related morphology” [7, 10]
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