Low prevalence of p16-positive HPV-related head-neck cancers in Thailand: tertiary referral center experience

Abstract

Background: There 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).

Methods: In 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.

Results: The 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).

Conclusion: A 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.

Keywords: Epidemiology; Head and neck cancer; Human papillomavirus (HPV); Laryngeal cancer; Oral cancer; Oropharyngeal cancer; Squamous cell carcinoma; Thailand; p16.

Fig. 1

Representative cases of NK, NK-M and K histological subtypes of OPSCC K cancer with sheets of compact cells (a), which are p16-positive (b) and HPV DNA ISH-positive (c). Inset shows intranuclear localization of HPV consistent with so-called “integrative” pattern of viral infection. NK-M case (d) is predominantly composed of compact cells mixed by areas with larger cells with more abundant eosinophilic cytoplasm (lower left); NK-M OPSCC are often p16-positive (e), but HPV ISH-negative (f). K carcinoma with typical keratin pearls (g), no p16 immunoreactivity (h), and no HPV ISH signal. Hematoxylin & eosin (a, d, g), p16 immunohistochemistry (b, e, h), high-risk HPV DNA ISH (c, f, i); semi-serial sections, × 100.

Fig. 2

Survival of patients with OPSCC. HPV-positive patients had significantly better survival compared to HPV-negative ones (a). OPSCC patients stratified by risk-of-death into low-, intermediate- and high-risk groups (b)