Protection of HIV-1 infected adolescents against HPV-related cancers in Africa

From the Galloway lab, Human Biology Division

Human Papilloma Virus (HPV) causes virtually all cervical cancers (types 16 and 18 represent 70% of the cases), 95% of anal cancers (mostly by type 16), 70% of oropharyngeal cancers (in majority type 16), and is a major cause of vaginal, vulval and penile cancers. Globally, 4.8% of all cancers are attributed to the HPV virus. The infection is common, and the virus is transmitted sexually. Several HPV vaccines have been developed and approved by the Food and Drug Administration and provide an efficient protection against new HPV infections. In developed countries, cytologic and HPV screening programs help reduce the burden of HPV-related cancers. In Australia, where the HPV vaccine is distributed for free by the government and vaccination is widely accepted, cervical cancer could be eliminated in the near future.  However, in most resource-limited countries such programs are not available and early HPV vaccination of adolescents in these areas would be the best protection against related diseases.

Illustration of HPV virus and the most prevalent cancer it causes: cervical cancer.
Illustration of HPV virus and the most prevalent cancer it causes: cervical cancer. Source: Scientific Animations (CC BY-SA 4.0),

Human immunodeficiency virus (HIV-1) infected populations are at particular risk for HPV-related cancers. Indeed, the immunodeficiency resulting from HIV-1 infection automatically sensitizes this population to persistent infection by HPV and may facilitate tumor escape from immune surveillance. The development and spread of Highly Active Anti-Retroviral Therapy (HAART) reduces the risk for HPV-associated malignancies, but the incidence is still greater in HIV-1 infected populations. In Africa, where most of HIV-1 infected children reside, a whole generation of infected children is reaching sexual maturity thanks to HAART, and thus will be highly exposed to HPV-infection and related diseases. These children would likely benefit from the HPV vaccine if the vaccine strategy was efficient despite HIV-1 infection. The work of Nelly Mugo (University of Washington), Dr. Anna Wald (Vaccine and Infectious Disease Division) and Dr. Denise Galloway (Human Biology Division), in collaboration with Dr. Dalton Wamalwa (University of Nairobi, Kenya), shows the efficacy of quadrivalent HPV vaccine, in HIV-1 infected girls and boys in Africa. The results of the clinical trial were published in the journal Vaccine in October.

Pre-adolescent (age 9-14) girls and boys, infected with HIV-1, were enrolled in the study. Patients received a first dose of quadrivalent HPV vaccine (qHPV, against types 6, 11, 16, 18) at enrollment, a second dose at month 2, a third and last dose at month 6. The assessment of qHPV vaccine efficacy was performed at month 7 and 12. Overall, 99 girls and 79 boys completed the twelve months of follow up.

In their study, Nelly Mugo and colleagues reported no serious adverse events related to vaccination, which confirmed the absence of toxicity of the vaccination strategy in HIV-1 infected patients after 12 months. Most importantly, at 7 months, the seroconversion rate (in this case the proportion of vaccinated patients who developed antibodies against a specific type of the virus) was superior to 93% for all four HPV types targeted by the vaccine, similarly to what was observed for HIV-1 infected US girls, or for HIV-1 negative adolescents from Kenya and Ghana. At month 12, the seropositivity rates were still superior to 90% for type 6, 11 ,16, and 72.5% for type 18, meaning that the qHPV vaccine is highly immunogenic. This is the first report demonstrating that qHPV vaccine is as efficient in HIV-1 infected adolescents in Africa compared to infected adolescents from developed countries (with higher standards of care) or HIV-1 uninfected adolescents (not immunosuppressed).

The authors also sought to assess the effect of HIV-1 infection stage on vaccine efficacy. Seven months after the first dose of vaccine was administered, HPV antibody titer was correlated to CD4 cell count (the fewer CD4 T cells the fewer HPV antibodies in circulation) and inversely correlated to plasma HIV-1 RNA. Even though HIV-1 related immunosuppression reduces the titer of HPV antibody, the seroconversion rate is so high that the authors do not expect that to be a limitation to the vaccine efficacy.

The authors point out that the World Health Organization and American Cancer Society recently approved a new schedule for HPV vaccine reducing the vaccination protocol from three to two doses, which may not be as efficient as the three-dose protocol in HIV-infected adolescents. Further studies are needed to confidently adopt the new recommended schedule in this particularly fragile population.

This work was supported by the Merck Investigators Study Program.

Fred Hutch/UW Cancer Consortium faculty members Drs Denise Galloway, Anna Wald, Jared Baeten, Connie Celum, Kenneth Ngure, Amalia Margaret, Linda Eckert and Nelly Mugo contributed to this research.

Mugo NR, Eckert L, Magaret AS, Cheng A, Mwaniki L, Ngure K, Celum C, Baeten JM, Galloway DA, Wamalwa D,Wald A. 2018. Quadrivalent HPV vaccine in HIV-1-infected early adolescent girls and boys in Kenya: Month 7 and 12 post vaccine immunogenicity and correlation with immune status. Vaccine. 36 (2018) 7025–7032. DOI: 10.1016/j.vaccine.2018.09.059.