The one–Jab revolution: how a Kenyan Trial rewrote the future of cervical cancer prevention

Author

Micah Sagini*

For a long time, cervical cancer has been a global health concern for women globally. Cervical cancer ranks fourth among cancer-related causes of death in women worldwide, with more than 500,000 new cases and around 300,000 deaths each year. Unlike most cancers, cervical cancer is caused by a virus known as human papillomavirus (HPV), which infects the human reproductive system. This virus is responsible for over 95% of cervical cancer cases [1]. 

The discovery of HPV as the cause of cervical cancer dates back to the 1970s when most scientists believed herpes simplex virus type 2 (HSV-2) was the cause of this malignancy. However, one scientist, Harald zur Hausen, was not convinced by this assumption. He proposed that cervical cancer might instead be caused by HPV. As often happens in science, his assumption, which challenged the then prevailing assumptions (linking herpes simplex virus type 2 with cervical cancer) was met with skepticism [2]. However, with determination and persistence, he demonstrated the presence of HPV types 16 and 18 in cervical cancer samples. His findings were later validated and widely accepted, leading to the development of HPV vaccines. Prof. Zur Hausen was awarded the Nobel Prize in Physiology or Medicine in 2008 for his groundbreaking discovery. The HPV types 16 and 18 are responsible for about 70–80% of all cervical cancer cases worldwide [3]. 

Normally, our immune system can clear up to 90% of HPV infections. However, in 10% of cases, the virus can evade the immune system and thrive in the female genital organs, leading to cervical cancer. The development of cervical cancer is driven by two viral oncogenes, E6 and E7, which promote cancer cell growth and survival [4].

Cervical cancer – a preventable malignancy

Following the discovery that HPV causes cervical cancer, several vaccines have been developed, including Cervarix (bivalent), Gardasil (quadrivalent), Gardasil 9 (nonavalent) and Cecolin. These vaccines can protect recipients from HPV types 16 and 18, which cause 70% of cervical cancer cases. Gardasil-9 can also protect against HPV strains 6, 11, 16, 18, 31, 33, 45, 52, and 58 [5, 6]. The HPV vaccines are designed from viral proteins expressed on the surface of the virus. These virus-like particles are harmless since they do not contain viral DNA. HPV vaccines, like other vaccines, confer protection by stimulating the body to produce antibodies against the virus. When these antibodies encounter the virus, they neutralize it, preventing it from infecting cells [7, 8].

The global HPV vaccination strategy

The World Health Organization recommends vaccinating girls and boys aged 9 to 14, ideally before sexual debut. The vaccination program is part of the organization's Immunization Agenda 2030, which envisions universal access to life-saving vaccines. The standard immunization schedule recommends two or three doses over 6 to 12 months [9]. This has proven challenging for many low-income developed countries, as they have to bear the high costs of immunization, deal with logistical hurdles, and increased cases of missed follow-up visits for subsequent doses. Therefore, completing two or three doses over 6 to 12 months for the intended age group has been challenging in low and middle-income countries, where cervical cancer cases are rising [10].

Could a single dose be enough? This question motivated researchers from the University of Washington, the Fred Hutchinson Cancer Center, and their Kenyan collaborators to initiate the study. The researchers commenced a clinical trial dubbed Kenya Single-dose HPV Vaccine Efficacy Study (KEN SHE). Their aim was to find out if a single dose of the HPV vaccine offers protection, as with two or three doses. Should this be the case, the implications would be enormous—cutting costs, simplifying delivery, and expanding vaccine coverage globally   

The KEN SHE TRIAL for young Kenyan women

The KEN SHE trial involved the recruitment of young Kenyan women aged 15 to 20 years. To be eligible, participants had to be HPV and HIV negative at enrollment and three months after. They were also required to have not been vaccinated against HPV and to be sexually active with one to five partners. For HIV protection, they were given pre-exposure medication. All these precautions were taken to ensure accurate results as HIV can impact the immune system [11, 12].

Out of 3090 screened participants, 2275 met the eligibility criteria. For vaccination, the participants were randomly assigned to receive either a bivalent, nonavalent, or Meningococcal vaccine, which served as the control. To prevent bias, a 'blinding approach' was implemented where neither the researchers nor the assistants knew, which vaccine each participant received. Samples were then collected at various intervals over 18 months for evaluation, with plans to extend follow-up for another 18 months to assess vaccine efficacy. At the end of the study, it was found that a single dose of the HPV vaccine (nonavalent or bivalent) conferred protection against HPV infection with 97.5% efficacy [11].

Why the KEN SHE study was important

In low and middle-income countries, teenage girls and young women are vulnerable to sexually transmitted infections, including HIV. HIV infection is particularly concerning because it weakens the immune system and increases susceptibility to persistent HPV infection. Therefore, a simplified, single-dose HPV strategy could reduce program costs, increase the rate of completed vaccination, expand access in rural and underserved regions and prevent hundreds of thousands of future cancer cases.

Conclusion

The outcome of the KENSHE study was a turning point in the fight against cervical cancer. By demonstrating the efficacy of a single HPV vaccine dose in protecting young girls against HPV infection, the study offers an alternative vaccination strategy to the multi-dose immunization approach. The single-dose immunization approach could, therefore, provide a practical, cost-effective solution for low- and middle-income countries. Simplifying immunization to a single dose could increase coverage, reduce healthcare barriers, and prevent cervical cancer cases globally. This research not only reshapes global cervical cancer prevention strategies but also brings us closer to equitable access to life-saving vaccines for all young women.

References

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