Human papillomavirus infection in healthy youth and in hypopharyngeal cancer

The aim of this thesis was to follow the prevalence of human papillomavirus in the oral cavity and in the cervix in youth during the period of 2008-2015, a period when HPV vaccination was gradually introduced to young girls in Sweden. In addition, we explored the prevalence of HPV in hypopharyngeal cancer during the period 2000-2012 on the basis that there has been an epidemic of HPV positive tonsillar and base of tongue cancer, which arise in locations with close physiological proximity to the hypopharynx.

The main questions addressed were whether HPV prevalence is similar within different cohorts of Swedish youth, how the prevalence changes over time and after the introduction of the HPV vaccines, and if the increased proportion of HPV positive oropharyngeal cancer is mirrored also in hypopharyngeal cancer. Since the prevalence of oral and genital HPV previously observed at a Stockholm youth clinic was high during the period of 2008-2011, there was an opportunity to compare these data to the HPV prevalence in different geographical locations and at other time points. The strong Swedish tradition of biobanking granted access to a relatively large sample of hypopharyngeal cancers, and the high prevalence of HPV in oropharyngeal cancers in Sweden made it credible that HPV would also be present at detectable levels in hypopharyngeal cancer and make it possible to detect changes occurring in the HPV prevalence in this cancer type.

To investigate these matters, oral and cervical samples were analyzed for the presence of HPV DNA, a questionnaire was used to investigate the sexual experiences of youth, and HPV DNA and p16 expression was analyzed in relation to survival in samples of hypopharyngeal cancer.

In Paper I, we could show that oral HPV prevalence was significantly less common in high school students from a middle sized municipality in Sweden (1.8%) than what was observed in 2009-2011 in the Stockholm youth clinic(9.3%).

In Paper II, we could show that there were no differences between HPV vaccinated and nonvaccinated women regarding condom use and self-reported STI history, however, vaccinated women were more likely to have had vaginal intercourse and one-night stands (p=0.005, and p=0.046, respectively).

In Paper III, we found a low oral HPV prevalence also at the Stockholm youth clinic (1.4%) in 2013-2014 which was lower than what was previously observed at the same clinic (p=0.00001). Cervical HPV 16, 31 and 70 prevalence was now less common in vaccinated than in non-vaccinated individuals (p =0.0002, p=0.019, and p=0.006, respectively).

In Paper IV, we expanded the cohort from paper 3 to also include samples from the fall of 2014 and the spring of 2015. Oral HPV prevalence remained low (1.5%) and cervical HPV 16, 31 and 6 were less common in vaccinated than in non-vaccinated women (p=0.0006, p=0.038 and p=0.009, respectively).

In Paper V, we could show that the proportion of HPV positive cases of hypopharyngeal cancer have not increased in Stockholm and that p16 is a poor surrogate marker of active HPV infection in this cancer type.

List of scientific papers

I. Nordfors C, Grün N, Haeggblom L, Tertipis N, Sivars L, Mattebo M, et al. Oral human papillomavirus prevalence in high school students of one municipality in Sweden. Scand J Infect Dis. 2013;(April):1–4.
https://doi.org/10.3109/00365548.2013.821626

II. Mattebo M, Grün N, Rosenblad A, Larsson M, Häggström-Nordin E, Dalianis T, et al. Sexual experiences in relation to HPV vaccination status in female high school students in Sweden. Eur J Contracept Reprod Health Care. 2014;19(2):86–92.
https://doi.org/10.3109/13625187.2013.878021

III. Grün N, Ährlund-Richter A, Franzén J, Mirzaie L, Marions L, Ramqvist T, et al. Oral human papillomavirus (HPV) prevalence in youth and cervical HPV prevalence in women attending a youth clinic in Sweden, a follow up-study 2013-2014 after gradual introduction of public HPV vaccination. Infect Dis (London, England). 2015 Jan;47(1):57–61.
https://doi.org/10.3109/00365548.2014.964764

IV. Grün N, Ährlund-Richter A, Franzén J, Mirzaie L, Marions L, Ramqvist T, et al. Follow-up on oral and cervical human papillomavirus prevalence 2013-2015 in youth at a youth clinic in Stockholm, Sweden. Infect Dis (London, England). 2016 Feb;48(2):169–70.
https://doi.org/10.3109/23744235.2015.1094573

V. Dalianis T, Grün N, Koch J, Vlastos A, Tertipis N, Nordfors C, et al. Human papillomavirus DNA and p16(INK4a) expression in hypopharyngeal cancer and in relation to clinical outcome, in Stockholm, Sweden. Oral Oncol. 2015 Sep;51(9):857–61.
https://doi.org/10.1016/j.oraloncology.2015.06.002