• Ivan Bristow

Can the HPV vaccine treat verrucae?


Mention the word vaccine or vaccination at the moment and it is a hot topic. Vaccination is a major step in combatting the spread of various infections. In the UK, it is over 12 years since the HPV vaccination was introduced for girls to protect against specific oncogenic strains of Human Papilloma Virus (HPV), responsible for most of the cases of cervical cancer. The vaccine was introduced in 2008 and according to studies is highly effective in protecting against cervical cancer and pre-cancers [1].





There are three HPV vaccines available which protect against two, four or nine types of the HPV virus. These are Cervarix® (HPV 16, 18 - bivalent), Gardasil® (HPV 6, 11, 16, 18 - quadrivalent) and Gardasil 9® (HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 - nonvalent). All of them protect against the two most common high-risk types of the virus: 16 and 18. These two strains are linked to over 70% of cervical cancers and 63% of penile cancers as well as most mouth, anus and throat cancers. Since 2012, Ceravix® has been dropped in favour of the Gardasil vaccines for immunisation by the NHS in the UK.


In 2008, the vaccination programme began in the UK for girls, initially and there was interest and hope in whether there could be any cross-protection against other types of HPV strains, for example, HPV strains causing cutaneous warts and verrucae [2]. Early reports suggested that cross-protection may occur over time in vaccinated individuals [3] and case studies presented showing patients clearing cutaneous lesions following HPV vaccination [4, 5]. This blog looks at a paper which has been published investigating this topic.


In a forthcoming publication in the Journal of the American Academy of Dermatology, Shin and colleagues [6] have published a study investigating the nonvalent vaccine. This was selected for this work as the newest of the vaccines, providing protection against 9 high-risk HPV strains, as it has been less studied and may provide more cross-protection against other types of HPV responsible for cutaneous warts. They recruited 45 people with multiple warts, which had been present for more than a year and had failed two previous therapies.


The average age of the cohort was 28 years old, and on average, they had 15 warts each. Around 57% were recorded as plantar warts. Patients received three doses of the vaccine at months 0, 2 and 6. Patients were reviewed at month 8, 2 months after receiving their final vaccination. Each wart was reported as “complete response”, “partial response” or “no response”. At the end of the study, 62% of patients had complete clearance (28 patients), 9% showed partial improvement (4 patients) and 29% had no response (13 patients). The mean time to respond was 12 weeks after the first vaccination. Interestingly the response rate in those above 26 was lower than for those 9 – 26 years of age (55% versus 84% respectively).


So, what can we learn from this work? Firstly, it's important to say this is a small-scale study but it demonstrates potentially that vaccination may work against verrucae. In this work 21 out of 26 patients had a complete or partial response. This was similar to an earlier, retrospective study by Yang et al., showing a slightly lower, 47% complete clearance [7]. To be sure though, much larger trials are needed with a robust design using a proper control group to be able to confidently say how effective it may be. Its also worth noting that age has a significant effect it would seem – the older patients in this study did not respond as well – this is typical for warts as we know children tend to shed their warts much faster than adults. This phenomenon has also been observed when vaccinating older adults using these vaccines against harmful HPV strains – antibody production is lower in older patients. Prior to this study, there have been case reports demonstrating wart regression following HPV vaccination. One paper showed five girls showing regression after vaccines from 6 months to 3 years afterwards [8]. However, with a time frame like that in secondary school-age children, it is difficult to argue if it was a vaccine effect or just natural, spontaneous regression which we know occurs in school-aged children. Previously published work showed that in children aged 11 with warts, only 7% will have them by the age of 16 – demonstrating this phenomenon [9].


The other piece of evidence may lie in real-world evidence. If schoolchildren have been vaccinated since 2008 in the UK, have we really seen a big drop off in the numbers of verrucae, particularly in children during that time? The answer, I think is probably not, suggesting that its effect may not be significant as we had hope for, but as ever, further research will fully answer this question.




References


1. Arbyn, M., et al., Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. The Cochrane database of systematic reviews, 2018. 5(5): p. CD009069-CD009069.

2. Martin, W.A., HPV vaccine may have role in wart treatment. BMJ, 2011. 343: p. d4351.

3. Ault, K.A., Human papillomavirus vaccines and the potential for cross-protection between related HPV types. Gynecologic oncology, 2007. 107(2 Suppl 1): p. S31-3.

4. Kreuter, A., T. Waterboer, and U. Wieland, Regression of Cutaneous Warts in a Patient With WILD Syndrome Following Recombinant Quadrivalent Human Papillomavirus Vaccination. Archives of Dermatology, 2010. 146(10): p. 1196-1197.

5. Daniel, B.S. and D.F. Murrell, Complete Resolution of Chronic Multiple Verruca Vulgaris Treated With Quadrivalent Human Papillomavirus Vaccine. JAMA Dermatology, 2013. 149(3): p. 370-372.

6. Shin, J.-O., et al., Nonavalent human papilloma virus vaccine for the treatment of multiple recalcitrant warts: an open label study. Journal of the American Academy of Dermatology, 2021.

7. Yang, M.Y., et al., Quadrivalent human papilloma virus vaccine for the treatment of multiple warts: a retrospective analysis of 30 patients. J Dermatolog Treat, 2019. 30(4): p. 405-409.

8. Martín, J.M., et al., Spontaneous Remission of Recalcitrant Warts in Girls After Human Papillomavirus Vaccination. Actas Dermosifiliogr, 2016. 107(6): p. 533-5.

9. Williams, H., A. Pottier, and D. Strachan, The descriptive epidemiology of warts in British schoolchildren. British Journal of Dermatology, 1993. 128.

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