HPV vaccination just keeps on giving

HPV vaccination has the potential to eliminate
 cervical cancer in future generations

As a keen follower of developments in cancer immunotherapy (and occasional commentator), it’s easy to forget the quiet impact of past advances in cancer treatment and prevention which are now a routine element of healthcare.

A publication from the Giovanni Lorenzini Foundation, a not for profit health educator,”HPV Vaccination Concepts in the Reality of Today”, reminded me that, while effective therapeutic cancer vaccines remain elusive, prophylactic vaccination against human papilloma viruses (HPV) has achieved the initial public health goal of significantly reducing the risk of cervical cancer and, in time, will have a similar impact on other HPV infection related cancers, notably cancers of the head and neck.

HPV infection is not uncommon, with viral DNA being detectable in around 10% individuals (and up to 30% in some populations). Over 200 types of HPV have been identified, with 15 or so being linked to cancer. These “high risk” types have a propensity to integrate their DNA with that of host cells, resulting in the expression of two particular proteins (E6 and E7) with cancer-causing potential. HPV-related cancers are a significant burden, accounting for an estimated 4.5% of all cancers, most commonly cervical cancer, followed by head and neck cancers, anal and male and female genital cancers.

Cervical cancer development is generally slow: the first HPV vaccines were deployed just over a decade ago so the absolute reduction in cancer cases is unknown. Meta-analysis of studies in women receiving either an HPV vaccine or a placebo found that pre-cancerous changes in the cervix were present in 2 of every 10,000 vaccinated women and in 164 of every 10,000 unvaccinated women. In women aged 15 to 26 years (but not those aged 25 to 45 years) vaccination reduced the risk of cervical pre-cancerous changes associated with the highest risk HPV types from 341 to 157 per 10,000. 

Early HPV vaccines were only capable of protecting against two or four high risk HPV types associated with cervical cancer, with vaccines introduced in the last four years addressing nine HPV types to provide broader protection against a range of HPV-related cancers, particularly head and neck cancers arising from or orpharyngeal infection with HPV. 

While the overall incidence of head and neck cancers is declining in developed economies, largely due to decreasing tobacco use, the incidence of HPV-positive cancers has risen over the last two decades. Extending routine HPV vaccination to young males (a policy in place in the UK since July 2018) should eventually reverse this trend, while also further reducing the prevalence of HPV-associated genital cancers.

HPV vaccination has not been without controversy. A meta-analysis of 73,000 participants in HPV vaccine studies did not encounter any evidence to support much publicized claims that “debilitating illness” (including rapid increase in heart rate on sitting or standing up- postural orthostatic tachycardia syndrome) was a common side effect in girls. The uptake of HPV vaccination in the US is low relative to overall vaccination rates. Parental concern that vaccination would somehow encourage promiscuity has been proposed as one reason, although studies suggest that lack of knowledge about the purpose and benefits of HPV vaccination; a three dose vaccine schedule which may have resulted in missing doses, and vaccine cost are key contributors.

HPV vaccination may have benefits outside of cancer prevention. The prevalence of HPV in seminal fluid is twice as high in infertile men when compared with the general population. Laboratory studies have identified several mechanisms by which HPV can detrimentally alter sperm, with the presence of sperm-bound viral DNA being a predictive factor for early miscarriage. Vaccination has been shown to increase the rate of HPV clearance from infected semen and might contribute to higher success rates for couples undergoing assisted reproduction.

Photo credit: chinnapong/shutterstock.com

Updated 30th June 2019:

Further evidence for the broad impact of HPV vaccination, with infection rates falling in older women and in men in countries with high vaccine uptake (three cheers for herd immunity) was published in the Lancet (and the subject of a press conference given in London) on the 26th June. 

Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Drolet, M et al.  The Lancet,online 26th June , 2019. https://doi.org/10.1016/S0140-6736(19)30298-3. Subscription or article purchase required. 

HPV vaccination concepts in the reality of today. Paderno, A et al. J Vaccines Vaccin 2019, 10:1 DOI: 10.4172/2157-7560.1000403 http://tinyurl.com/y4t82ke4 (Open Access).

Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Arbyn, M et al. Cochrane Systematic Review - Intervention Version published: 09 May 2018. http://tinyurl.com/yyugyaz5 (Open Access).