A new lead study by researchers in the United States has revealed that human papillomavirus (HPV) is an important cause of oropharyngeal cancer (OP) not just in men but also among women, and contributes for a small proportion of non-OP head and neck squamous cell cancers.
Most of the epidemiological studies over the decades on head and neck squamous cell cancer (HNSCC) have found that its occurrence has altered dramatically. In the case of oral cavity and laryngeal squamous cell cancers, the occurrence has declined, while oropharyngeal squamous cell carcinoma (OPSCC) – particularly caused by human papillomavirus (HPV) – has increased in white men with less than 60 years of age. Moreover, the occurrence of OPSCC has decreased among women and elderly black men while it remains stabilized in Asians and Hispanics. Therefore, the role of HPV in OPSCC remains uncertain, and OPSCC has lower incidence in women and nonwhites. In general, most of the studies on cancer to date have been evaluated based on gender, race and sample size, but in the case of OPSCC, the non-quantitative polymerase chain reaction method has been employed for HPV detection. Moreover, prevalence of HPV has been evaluated for determining the true etiologic agent in HNSCCs arising outside the oropharynx (OP). Since the prevalence of HPV among other demographic groups and its impact on other anatomic sites of HNSCC is unclear, a study by Souz and co-researchers of Johns Hopkins School of Medicine, United States was conducted, and the findings were published in the journal JAMA Oncology in 2016.
A retrospective cohort study was carried on 863 subjects suffering from squamous cell cancer of the oral cavity, oropharynx, larynx, or nasopharynx from 1995 to 2012 to explore the HPV tumor status in OPSCC and non-oropharyngeal (non-OP) HNSCC among women and nonwhite men. The status of the tumor in HPV was measured by p16 immunohistochemical analysis, HPV16 DNA in situ hybridization (ISH), and high-risk HPV E6/E7 mRNA ISH. Among the 863 subjects suffering from HNSCCs, it was observed that 27.8% had cancer of OP, oral cavity (29.3%), larynx (28.4%) and nasopharynx (14.4%). In the case of OPSCCs, 60% of the subjects were found to be p16 positive (p16+), 48% were HPV16 DNA ISH positive (ISH16+), and 56% were positive for any oncogenic HPV type (ISH+). Interestingly, the proportion of p16+ in OPSCCs has increased significantly among women and men, as well as among whites and nonwhites. In case of non-OP HNSCCs, a higher proportion was notice in p16+ when compared with ISH+. A high proportion of p16+ in sites of the oropharynx was observed in non-OP HNSCCs. Over time, the proportion of non-OP HNSCCs showed increase in p16+ (or ISH+) among whites but not among nonwhites. Among OPSCCs, P16+ had high sensitivity and specificity while this was negative for ISH+. In non-OP HNSCCs, p16+ had lower sensitivity and positive predictive value but high specificity and negative predictive value for ISH positivity.
In short, research demonstrates that HPV is an important cause for the onset of OPSCC and identifies both p16 and ISH tests as appropriate methods for the identification of OPSCC caused by HPV. In addition, the study has several limitations in terms of demographic and clinical information, as well as anatomic sites considered for estimating HPV. However, the clinical aspects of HPV indicates that it is an important cause of OPSCC among women and nonwhite minorities in the United States.
Written By: Manche Santoshi, PhD