While a vaccine exists to prevent human papillomavirus (HPV), the main cause of cervical cancer, over 20 therapeutic HPV vaccine candidates are currently in development.

These therapeutic vaccines aim to “boost the body’s immune response so that it can either fight and clear high-risk strains of the virus or abnormal ‘precancerous’ cells,” according to the World Health Organization (WHO).

The global body issued a report on Wednesday to guide vaccine developers about the preferred product characteristics (PPCs) for any new therapeutic vaccines in priority disease areas – primarily low and middle-income countries (LMICs).

Eliminating cervical cancer, which kills one woman every 90 seconds,  is a major public health initiative for WHO. The key goals of its current strategy are to vaccinate 90% of girls with preventive vaccines, screen 70% of women with a high-performance tests like DNA screening, and treat 90% of women with cervical cancer or precancerous cells in the cervix by 2030.

Millions of adults have missed out

A therapeutic vaccine “is likely to be especially beneficial for adult women who did not receive the HPV vaccination before contracting the virus and in poorer countries, where millions of women still lack access to effective cervical screening and cancer treatments,” according to WHO.

Currently, the HPV preventive vaccine is targeted at school children before they become sexually active. Most countries offer it to boys too as they can carry HPV and infect girls and women.

Only 28 of the 47 countries in the WHO African Region, the region with the highest rates of cervical cancer, had introduced prophylactic HPV vaccine into their national immunisation programmes by January.

Africa’s most populous country, Nigeria, introduced the vaccine in parts of the country last October. Others do not yet have it as part of their immunisation programme. 

This means that millions of adult women are not vaccinated. In addition, many women do not get screened for HPV, while others might be diagnosed with pre-cancerous cells or cervical cancer yet not get access to treatment.

Complementary vaccines

“Therapeutic HPV vaccines could be a catalytic innovation that complement these existing interventions, increasing options for the millions of women who have already acquired HPV and reducing their risks of developing life-threatening cancer in the future,” said Dr Sami Gottlieb, a medical doctor and epidemiologist at WHO’s Department of Sexual and Reproductive Health and Research. 

An expert group convened by the WHO identified that therapeutic vaccines would be useful in places where it has been difficult to scale up cervical cancer screening and treatment, and as “an alternative, simpler treatment to reduce loss to follow-up” of women who are effectively treated following a positive test. 

“A wide variety of approaches have been used to develop therapeutic HPV vaccine candidates, including peptide, protein, DNA, RNA, and bacterial- and viral-vectored vaccine platforms,” according to WHO.

Vaccine candidates have mainly targeted the regression of CIN2/3 lesions and invasive cervical cancer, while a few candidates focusing on clearance of high-risk HPV infection are now in phase 1 and 2 studies.

‘Therapeutic HPV vaccines would ideally have high efficacy in both clearing high-risk HPV infection to prevent development of cervical precancers, and treating high-grade precancers that have already developed,” according to WHO. 

At a minimum, first-generation vaccines would be expected to clear infection and/or prevent high-grade cervical precancer due to HPV types 16 and 18, according to WHO.

These vaccines could be given to adult women through population-based vaccine delivery – without a diagnostic test if that was not available. 

Therapeutic HPV vaccines that could reverse the progression of high-grade cervical precancers (at a minimum HPV 16 and 18) could be used as an alternative or adjunct to existing cervical treatments in women with cervical precancer according to positive screening tests. 

“Both types of vaccine could potentially play a role in addressing each of the identified gaps in cervical cancer prevention programmes. 

“The choice of target population, including the optimal age range and the delivery strategy in a given setting, will not only depend on intrinsic vaccine characteristics – such as efficacy in clearing infection rather than causing regression of high-grade precancers – but also on factors related to the environment into which these vaccines are introduced.”

Image Credits: Tom Pietrasik/ WHO.