The most important factor in almost all cervical cancers is persistent infection with high-risk HPV. While HPV types 16 and 18 cause 70% of cervical cancers worldwide; Types 31, 33, 45, 52 and 58 additionally account for in 20% of cervical cancers. In addition, HPV 16 and 18 are causative factors in 90% of anal cancers. HPV also plays an important role in oropharyngeal, vulvar and vaginal cancers. HPV 6 and HPV 11 are isolated in 90% of the genital warts, which are the most frequently observed lesions related to HPV and affect patients not only physically but also psychologically and socially.
In order to reduce the burden of disease associated with HPV, three types of HPV vaccines have been developed and made available to date. Current HPV vaccines are prophylactic and are produced with recombinant technology. Developments on therapeutic HPV vaccines are ongoing and are at an experimental stage.
Today, when preparing prophylactic HPV vaccines, the virus’s L1 gene is inserted into a host (yeast or baculovirus), thereby producing an excessive amount of L1 protein. These L1 proteins become virus-like particles (VLP). VLPs are similar to HPV in shape and size, but since they do not contain viral DNA, they are not infectious or oncogenic.
There are three types of HPV vaccines available on the market:
Bivalent vaccine (CervarixTM) [Contains VLP for HPV type 16 (20 μg) and 18 (20 μg)];
Quadrivalent vaccine (Gardasil TM) [Contains VLP for HPV type 6 (20 μg), 11 (40 μg), 16 (40 μg) and 18 (20 μg)]
Nonavalent vaccine (Gardasil-9 TM) [Contains VLP for HPV type 6 (30 μg), 11 (40 μg), 16 (60 μg), 18 (40 μg), 31 (20 μg), 33 (20 μg), 45 (20 μg), 52 (20 μg) and 58 (20 μg)].
Although these three vaccines are in use worldwide, all three may not be available in every country. As of April 2020, while bivalent and quadrivalent HPV vaccines are available in our country, efforts are ongoing for the introduction of nonavalent vaccine.
Indications and Usage
HPV vaccine has not yet entered the national vaccination program in our country. Routine HPV vaccination is recommended in the USA at the age of 11-12. HPV vaccine can be given as early as age 9. Catch-up vaccination is recommended in girls 13-26 year old who have not previously vaccinated or completed the vaccine series. These suggestions are valid in the US and Europe.
For countries with limited resources, the World Health Organization (WHO) recommends that the primary target in the HPV vaccination program is girls aged between 9-14.
Nonavalent HPV vaccine has been approved by the FDA in women up to age 45 years. Although routine vaccination is not recommended for ages 27 and beyond, an individualized decision should be made for this age group. In January 2020, Advisory Committee on Immunization Practices (ACIP) stated that HPV vaccination can be recommended to adults aged 27-45 years old who have not previously been vaccinated or who have not completed the vaccination schedule; considering personal risk factors and possible benefits from the vaccine in adults.
In our practice, we recommend vaccination up to the age of 45 topatients who do not have any adverse factors that would preclude HPV vaccination in their medical history.
Vaccine preference is a controversial and frequently asked topic. First of all, it is worth noting that all three vaccines are not found everywhere. As of April 2020, nonavalent vaccine is not commercially available in Turkey. Due to the 5 additional types of HPV that the nonavalent vaccine provides protection but the bivalent and quadrivalent vaccines do not, the nonavalent vaccine if available, may be preferred in women. In men, it is uncertain whether the nonovalent vaccine will provide additional protection against cancer.
For those who are 15 years old and under, two doses of vaccination are recommended (at 0 and 6th-12th months), and three doses of vaccination at 0, 1st-2nd and 6th months is recommended for older ages. In immunocompromised individuals, three doses of vaccination are recommended, regardless of age, at 0, 1st-2nd and 6th months.