Abstract
BackgroundThere is a dramatic rise in the incidence of Human papillomavirus (HPV) – associated head and neck squamous cell carcinoma (HNSCC) in the world, with considerable variation by geography, gender and ethnicity. Little is known about the situation in Bangladesh, where tobacco- and areca nut-related head and neck cancers (HNCs) are the most common cancers in men. We aimed to determine the prevalence of HPV in HNSCC in Bangladesh and to explore the possible value of cell cycle markers in clinical diagnostic settings.MethodsOne hundred and ninety six archival HNSCC tissue samples were analysed for the presence of HPV DNA. The DNA quality was assured, and then amplified using a nested PCR approach. The typing of HPV was performed by automated DNA sequencing. Cellular markers p53, Cyclin D1 and pRb were tested on all samples by immunohistochemistry (IHC), as well as p16 as a putative surrogate for the detection of HPV.ResultsHPV DNA was detected in 36/174 (~21%) samples: 36% of cancers from the oropharynx; 31% of oral cancers, and 22% from the larynx. HPV-16 was most common, being present in 33 samples, followed by HPV-33 (2 samples) and HPV-31 (1 sample). Twenty-eight out of 174 samples were positive for p16, predominantly in HPV-positive tissues (p < 0.001). No statistically significant association was observed between the cellular markers and HPV DNA positive cases. However, p16 positivity had excellent predictive value for the presence of HPV by PCR.ConclusionThere is a significant burden of HPV-associated HNSCC in Bangladesh, particularly in the oropharynx but also in oral and laryngeal cancers. Whilst a combination of PCR-based DNA detection and p16 IHC is useful, the latter has excellent specificity, acceptable sensitivity and good predictive value for carriage of HPV in this population and should be used for prognostic evaluation and treatment planning of all HNSCC patients in South Asia, as in the Western world.
Highlights
There is a dramatic rise in the incidence of Human papillomavirus (HPV) – associated head and neck squamous cell carcinoma (HNSCC) in the world, with considerable variation by geography, gender and ethnicity
One-third of the total head and neck cancers (HNCs) cases in the world have been shown to be associated with high-risk HPV infection, but wide geographic variation exists [9, 11]
Presence of HPV DNA and HPV type Overall, 36/174 (~21%) of blocks were positive for HPV DNA
Summary
There is a dramatic rise in the incidence of Human papillomavirus (HPV) – associated head and neck squamous cell carcinoma (HNSCC) in the world, with considerable variation by geography, gender and ethnicity. Head and neck cancer (HNC) is a major health problem worldwide, with an annual incidence of approximately 600,000 cases and close to 300,000 deaths, mostly in less developed countries (GLOBOCAN 2012) [1]. HPV-associated HNSCC represents a distinct entity with increase in incidence over the last three decades, mostly in developed countries and commonly affecting young adult males who tend to be non-smokers, non- or light- drinkers and many have relatively high socioeconomic status [6]. One-third of the total HNC cases in the world have been shown to be associated with high-risk HPV infection, but wide geographic variation exists [9, 11] Because HPV-related HNC patients have significantly better treatment response and 3-year overall survival rates (82.4% vs 57.1%) irrespective of age, gender or tumour stage [9, 10], knowledge of HPV status is mandatory in most tumour boards for the planning of treatment.
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