Vulvar and vaginal cancers are relatively rare tumours worldwide, with 44,000 and 17,500 new cases estimated in 2018 respectively; together they comprise less than one-half of a percent of the global cancer incidence. Rates of both cancers tend to be elevated in the high-income countries of Europe, North America and Oceania (http://gco.iarc.fr). The highest age-standardised incidence (world) rates (ASR) for vulvar cancer are observed in several German populations (ASR between 4 and 6), whereas for vaginal cancer, numbers are very small (ASR <1/100000), with rates somewhat higher among black populations in the U.S. and several indigenous populations in the U.S., Canada and New Zealand (http://ci5.iarc.fr). Survival, where measured (in highincome countries), is estimated at 50-70% for these tumours, and mortality is consequently lower (about 15,000 vulvar, and 8,000 vaginal cancer deaths worldwide). The proportion of cancers linked to HPV markedly differs between the two sites and by region¹. A high proportion of vaginal cancers are associated with HPV (78%), whereas for vulvar cancer, the proportion positive for HPV is much lower (25%).

There is increasing interest in these tumours, in part sparked by the prospect that, as with the changing paradigm of oropharyngeal cancer, increasing incidence trends and improving survival are driven by increasing oncogenic HPV infection. Figures 1 and 2 compare incidence trends in vulvar and vaginal cancers in selected registry populations at diagnostic ages 30- 69, with, for comparative purposes, trends in cervical cancer. In Figure 1 – countries with strong cervical cancer preventative programmes and increasing oropharyngeal cancer – vulvar cancer incidence rates are moderately increasing, at least in Australia, Norway and the U.K., with rates in the U.S. more stable. Vaginal cancer incidence rates are uniformly lower and the trends reasonably stable or in decline. In Figure 2 – countries with historically high or increasing cervical cancer incidence – the trends in vulvar and vaginal cancer appear mainly flat and parallel; there are signs of longer-term minor declines in both cancers in Colombia (Cali) and India (Chennai, where vaginal rates exceed those of vulvar), while recent increases in Slovakia and China (Shanghai) are speculative.

One caveat is that analyses are for all vulvar cancers (as in Figures 1 and 2) not just the predominant histological type, squamous cell carcinoma (SCC); this may impact on the magnitude of the temporal trend and comparability with other studies. Nevertheless, the main finding here mirrors the emerging evidence of an increasing incidence of vulvar cancer in certain populations. A review of incidence trends 1988-2007 reported increasing rates in 13 countries,² while a number of studies have highlighted temporal increases in England, the Netherlands, Norway, the U.S. and Australia. Common to these reports is the finding that significant increases in trends are restricted to highincome countries (e.g. also included were Canada, Denmark, France, Germany, Iceland, Ireland,

Sweden, Switzerland, United Kingdom and Japan in Kang et al)² and to certain younger age groups (aged 20-69). In the 13-country review², increases in women were confined mainly to ages 2

In a recent meta-analysis, women with HPVpositive vulvar cancer had a higher overall and disease-free survival compared to HPV-negative women with the disease.³ Alongside rising incidence rates of vulvar cancer, corresponding increases in survival from vulvar cancer may be expected, if there is an increasing proportion of cases associated with high-risk HPV. Reports thus far have been mixed: with incidence rates on the rise, 1- and 5-year vulvar cancer survival proportions have improved in England,⁴ but not in the Netherlands.⁵

In summary, there is mounting evidence of moderately increasing incidence rates of vulvar cancer among younger women in high-income countries, linked to generational changes in sexual behaviour and increasing high-risk HPV. In contrast, vaginal cancer incidence rates are lower and appear rather stable.

Irrespective of the trends, the future scenario is likely an increasing number of cases of both cancer types as population ageing and growth continues; more optimistically, the promise of high-coverage HPV vaccination should counter the rising burden eventually, and begin to prevent cases, starting at younger ages of diagnosis.

References

1. de Martel C, Plummer M, Vignat J, et al. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer 2017;141:664– 70. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520228/
2. Kang Y-J, Smith M, Barlow E, et al. Vulvar cancer in high-income countries: Increasing burden of disease. Int J Cancer 2017;141:2174–86. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28730615
3. Rasmussen CL, Sand FL, Frederiksen MH, et al. Does HPV status influence survival after vulvar cancer? Int J Cancer 2018;142:1158–65. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29090456
4. Lai J, Elleray R, Nordin A, et al. Vulval cancer incidence, mortality and survival in England: age-related trends. BJOG 2014;121:728–38. Available form: https://www.ncbi.nlm.nih.gov/pubmed/24148762
5. Schuurman MS, van den Einden LCG, Massuger LFAG, et al. Trends in incidence and survival of Dutch women with vulvar squamous cell carcinoma. Eur J Cancer 2013;49:3872–80. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24011936