We are treating increasingly more patients with head and neck cancer. The incidence of OPC has been rising in New Zealand since 2005,1 and a retrospective review over a 20-year period to 2010 shows almost fourfold greater incidence in men (1.87 per 100,000) than in women (0.47 per 100,000).2
Over the last several years, the traditional risk factors for head and neck cancers, such as smoking and alcohol consumption, have been replaced by HPV infection for OPC. Our study investigating the changing prevalence of HPV-positive OPC in patients residing in the greater Wellington region demonstrates a tripling of the proportion of HPV-positive OPC over the 20-year period.3
Patients with HPV-positive OPC are 10 years younger than those with HPV-negative OPC, and they are less likely to have smoked.3 The study confirms the increased prevalence of HPV-positive OPC in New Zealand and demonstrates its disproportionate burden on men, which is in keeping with other developed nations, such as Australia,4 the US5 and Sweden.6
In 2018, there were an estimated 95 new OPC cases and 25 OPC-related deaths in New Zealand.7 However, a recent national survey shows there were 315 HPV-positive and 53 HPV-negative new OPC cases in 2020 (unpublished data). This compares with the approximately 190 women diagnosed with cervical cancer and 72 related deaths each year.
The oropharyngeal region, which includes the tonsils, base of tongue, soft palate and pharyngeal walls, is the most studied in terms of causality with HPV.8,9
HPV can be transmitted by skin-to-skin contact or oral sex. Although the rate of HPV infection is high, most people infected do not develop cancer. For the majority, HPV infection is transient and becomes undetectable within one year, although it may remain latent and become reactivated many years later. Recurrent HPV infection can also occur.10
There are more than 150 distinct subtypes of HPV, which are grouped according to their oncogenic capacity as high risk and low risk, with some low-risk subtypes found to cause benign conditions, such as genital warts. High-risk HPV subtypes, such as HPV16 and HPV18, play a significant role in lower genital tract pre-cancers and cancers: cervical (almost 100 per cent), vaginal (~90 per cent), anal (~80 per cent), penile (~50 per cent) and vulval (~40 per cent); plus oropharyngeal (~75 per cent).11
It is unclear why the oropharynx is more susceptible to HPV-induced cancer than other head and neck sites. One reason may be that the oropharynx, cervix and anogenital regions offer easy access for infection. The tonsils, which contain deep invaginations of the mucosa, may facilitate viral access to basal cells.
HPV is a double-stranded circular DNA virus. Viral integration into the host genome at random sites is important for malignant transformation. This linearises the HPV genome, interrupting the viral DNA within the E1/E2 open reading frame, resulting in a loss of the E2 viral repressor and overexpression of E6 and E7 oncogenes.12
The E6 protein degrades p53, the Guardian of the Genome, resulting in activation of telomerase reverse transcriptase and immortalisation of cells. The E7 protein binds to retinoblastoma protein – a tumour suppressor protein – removing its antitumour mechanism. The E7 protein also possibly activates cyclins E and A, which are involved in the cell cycle.12
The result of HPV infection with high-risk HPV subtypes is oncogenic proteins that disrupt inherent antitumour protective mechanisms, allowing a fertile bed for malignancy to develop, especially in concert with environmental factors.12
A 2017 New Zealand study found that just under 80 per cent of OPC cases identified from the cancer registry were attributable to HPV, 98 per cent of which are due to HPV16.13