I haven’t forgotten about my summer resolution to go through my pile of papers and Firefox tabs waiting to be read. In fact, I have now gone through quite a few of them, but there is never enough time to write about it, at least not in depth. Also, new interesting studies keep getting in the way … Here is now something that I really wanted to write about: the link between HPV and head and neck cancer.
Some time last fall I read a news article in Nature about human papilloma virus (HPV), and the associated risk of cancer. The article was not simply about the recognized link between HPV and cervical cancer, but it also (and mostly) talked about the growing body of data implicating HPV in a large proportion of head and neck cancers.
HPV is the most common sexually transmitted infection in the US. Multiple strains exist, and altogether HPV viruses are so common that, according to the Center for Disease Control and Prevention (CDC), nearly all sexually active men and women become infected at some point in their lives. Public health campaigns recommending women to have regular Pap tests (which look for changes on the cervix that might lead to cervical cancer) as well as recommendations for girls and young women to receive HPV vaccination have contributed to inform the public that certain types of HPV can cause cervical cancer. In fact, it is estimated that up to 70% of all cervical cancers are caused by two high-risk strains alone, HPV types 16 and 18.
What is less known is that HPV can also cause oropharyngeal cancer.
Until the late 90’s, cancer in the back of the throat most often occurred in people who were long-term drinkers and smokers. Then another trend emerged: more and more cases occurred in healthier, younger people, with no history of heavy smoking/drinking. These cancer cases also looked a bit different in their prognosis and biology: when treated with chemotherapy and radiotherapy, the patients had a better survival rate ; the tumor appeared located at a slightly different site in the throat (originating deep in the tonsils rather than on the surface), and many lacked mutations in the tumor suppressor protein p53 (usually a hallmark of oropharyngeal cancer).
Maura Gillison, a researcher at Johns Hopkins University in Baltimore, started working on the topic of HPV and head and neck cancer in the late 90’s. She found that HPV was present in many tumor samples from patients with head and neck cancer, and in 2000, she and her colleagues published a study showing that there was indeed a distinct type of oropharyngeal cancer associated with the presence of HPV: the tumor started deep in the tonsils, HPV DNA was present in tumor cells, there were fewer p53 mutations than in HPV-negative cancers, the survival rates were better, and there was less association with alcohol and tobacco use. In 2007, Gillison and her colleagues published a large population study in The New England Journal of Medicine showing that people with oropharyngeal cancer were much more likely to be infected with HPV in their mouths and throats than people without.
Since then, more evidence has emerged indicating that HPV causes a large proportion of head and neck cancers. In fact, both the proportion and the number of HPV-positive oropharyngeal cancers seem to be on the rise (see graph in the Nature news article here). The reason why is unknown, but one suggestion is the increase in the average number of sexual partners in the population.
HPV is a common pathogen, and a study published in 2007 found that about 27% of a sample of 1921 American women aged 14 to 59 years tested positive for one or more strains of HPV (the prevalence of HPV was highest in women aged 20-24). About 3.4% of women tested positive for the HPV types targeted by the vaccine Gardasil (types 6, 11, 16, and 18). However, the limitations of this study were doubled: first, such a snapshot of HPV prevalence in the population at a given time point does not say anything about total lifetime exposure to HPV for individual women ; second, testing positive for a high-risk strain of HPV at one time point does not inform much on the risk of developing cervical cancer. Indeed, in most cases the immune system clears the HPV infection on its own, and what matters for a high-risk type of HPV to lead to cervical cancer is the persistence of infection (how long the virus remains active).
Since HPV infection is common and often goes unnoticed, and since there is no way to know whether infection will lead to cancer, scientists and public health bodies underscore the importance of routine cervical cancer screening with Pap tests. However, there is currently no good equivalent screening test for HPV-caused head and neck cancer : since HPV-positive oropharyngeal cancer starts deep in the tonsil, any screening test would require an invasive procedure.
HPV vaccines have been developed in recent years, and the CDC currently recommends vaccination for both girls and boys aged 11-12, and catch-up vaccines for males up until 21 and females up until 26 years of age. The World Health Organization recommends vaccination for girls aged 9-13 years (the whole point being that vaccination is most effective when received prior to exposure to HPV, and therefore before becoming sexually active). Long-term surveillance programmes will monitor uptake of HPV vaccination in the population, record any potential adverse effect (see CDC for example), and evaluate its benefits, notably its impact on rates of HPV-caused cancers, to allow optimization of public health policies (one such study here).
HPV: Sex, cancer and a virus. Megan Scudellari. Nature. 20 Novembre 2013. doi: 10.1038/503330a
Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D. J Natl Cancer Inst. 2000 May 3;92(9):709-20. doi: 10.1093/jnci/92.9.709
Case-control study of human papillomavirus and oropharyngeal cancer. D’Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML. N Engl J Med. 2007 May 10;356(19):1944-56. doi: 10.1056/NEJMoa065497
Prevalence of HPV Infection Among Females in the United States. Dunne EF1, Unger ER, Sternberg M, McQuillan G, Swan DC, Patel SS, Markowitz LE. JAMA. 2007 Feb 28;297(8):813-9. doi: 10.1001/jama.297.8.813
Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study. Tabrizi SN, Brotherton JM, Kaldor JM, Skinner SR, Liu B, Bateson D, McNamee K, Garefalakis M, Phillips S, Cummins E, Malloy M, Garland SM. Lancet Infect Dis. 2014 Aug 5. pii: S1473-3099(14)70841-2. doi: 10.1016/S1473-3099(14)70841-2