Cervical cancer is a major morbidity worldwide. [1] Most cancers are preventable by effective screening, and cervical cancer screening, arguably, best meets the Wilson criteria for a screening programme. Understanding the biology of the disease underpins and informs effective cervical screening, and this understanding has advanced greatly since I first was involved in the UK programme (in 1989). Most importantly, understanding the obligate role of persistent infection by high risk human papillomavirus (hr-HPV), particularly HPV type 16, in the genesis of most cervical cancers has led to the introduction of HPV testing for screening and to the production and delivery of vaccines against clinically relevant hr-HPV.

The protective effect of hr-HPV immunisation was shown in clinical trials using the bivalent and quadrivalent vaccines. [2] The bivalent vaccine is directed against HPV 16 and 18, the most important high risk types. The quadrivalent vaccine also generates immunity against two low risk types (HPV 6 and 11) that cause genital warts. [3-5] Real life data from Australia (quadrivalent vaccine) and Scotland (bivalent vaccine), have shown that both vaccines are highly effective in preventing HPV infection and its consequences: preinvasive cervical disease and genital warts. Furthermore, herd protection is unequivocal, as HPV infection, genital warts, and cervical disease have also decreased since immunisation programmes started in women and men who have not had the vaccine. [3-6] No evidence has been found for HPV “fighting back” by either type replacement (other hr-HPV becoming more prevalent in important disease) or mutation (HPV has a low mutation rate). Finally, the data show that the bivalent vaccine is associated with significant cross protective immunity against three other important hr-HPV types—31, 33, and 45—that are related to HPV 16 and 18, making it effectively a pentavalent vaccine. UK epidemiological data have shown that HPV 16, 18, 31, 33, and 45 alone are associated with 90% of cervical cancers. [7]

The most recent population based data from Scotland reinforce the message that the vaccine is having a considerable and sustained effect, showing that women who were immunised at age 12-13 have virtually no high grade disease when screened eight years later. [8] One of the implications of this work is that considerably fewer women will have to live with the physical and psychological implications, including pregnancy loss, of colposcopy and treatment. Globally, millions of doses of HPV vaccine have been given to females and, increasingly, males. In Scotland, as elsewhere, no serious adverse effects have been demonstrably linked to the vaccine. The ratio of benefit to possible harm therefore strongly supports HPV immunisation.

In the context of a professional life in which cervical screening has been a major part, this is remarkable news. The anxiety caused by the inherent subjectivity of reading a cervical smear, and therefore the follow-up of abnormalities of uncertain significance, has been a major concern. Even the move to HPV testing as the primary screening test does not get around these problems. Neither method of screening is feasible in low and middle income countries, which shoulder the greatest burden of cervical cancer

HPV immunisation therefore offers the only feasible solution to preventing a cancer the cause of which is well established—hr-HPV infection—in those areas of the world where the burden of the disease is greatest. It is also the most cost effective method in developed countries. This a veritable triumph for medicine.

Tim Palmer is clinical lead for cervical screening in Scotland and is based at the Department of Pathology, University of Edinburgh, Edinburgh, UK

Competing interests: See research paper

References:

1. GLOBOCAN Cervical cancer fact sheet http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx accessed 21 May 2018
2. Arbyn M, Xu L, Simoens C et al, Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database of Systematic Reviews 2018, Issue 5. Art. No.: CD009069.
3. Garland S, Kjaer S, Muñoz N et al. Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-world Experience. Clin Infect Dis 2016; 63: 519-27.
4. Pollock KG, Kavanagh K, Potts A, et al. Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland. Br J Cancer 2014; 111: 1824-30
5. K. Kavanagh, K Pollock,K Cuschieri et al. Changes in the prevalence of human papillomavirus following a national bivalent human papillomavirus vaccination programme in Scotland: a 7-year cross-sectional study Lancet Infectious Diseases 2017; 17:1293-1302
6. Cameron R, Kavanagh K, Pan j, et al Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009–2013 Emerg Infect Dis 2016 22(1): 56-64
7. Mesher D, Cuschieri K, Hibbits S et al. Type-specific HPV prevalence in invasive cervical cancer in the UK prior to national HPV immunisation programme: baseline for monitoring the effects of immunisation. J Clin Pathol 2015; 68: 135-40
8. Palmer T, Wallace L, Pollock K, et al Prevalence of cervical disease at age 20 following bivalent HPV vaccination at age 12-13  in Scotland: a retrospective population study BMJ2018.047003 in press