Canadian study finds HPV vaccine beneficial for HIV-positive women

• A new study followed 279 Canadian women with HIV vaccinated against HPV
• Researchers compared HPV incidence to studies with other groups of women
• The vaccine offered protection, but not as much as for HIV-negative women

Human papilloma virus (HPV) is a relatively common sexually transmitted infection. In women, HPV can cause the development and growth of abnormal cells in the cervix, vulva, anus, mouth and throat. In time, some of these abnormal growths can transform into pre-cancers and, in some cases, cancer.

HIV infection weakens the immune system and studies have found that HIV-positive women are more likely to have HPV infection than HIV-negative women. Studies have also found that HIV-positive women are at heightened risk for the growth and development of abnormal cells in the cervix and for invasive cervical cancer.

There are three approved HPV vaccines, as follows:

• Cervarix – provides protection against HPV strains 16, and 18; these cause about 70% of cervical cancers
• Gardasil – provides protection against HPV strains 6 and 11 (these cause ano-genital warts) and also against strains 16 and 18
• Gardasil 9 – provides protection against nine strains of HPV, including 6, 11, 16 and 18, and five other strains that cause cancer: 31, 33, 45, 52 and 58

In a Canadian study called CTN 236, researchers used Gardasil (which was the vaccine available at the time the study started that provided the broadest coverage against HPV) in 279 HIV-positive women and girls. These participants were monitored for about two years after vaccination. For purposes of comparison, researchers used data from previously published research.

In the present study, researchers found the following:

• HIV-positive vaccinated women experienced rates of persistent HPV-related disease at similar rates as HIV-negative women who were not vaccinated. However, the researchers stated that the rate of persistent infection with HPV strains 6, 11, 16 and 18 in the present study “is substantially lower” among vaccinated HIV-positive women compared to unvaccinated HIV-positive women in another study.
• No cases of highly abnormal cervical pre-cancer and cancer occurred among HIV-positive women.

Overall, rates of vaccine failure were low in the present study, but researchers suggested that there is the possibility that some HIV-positive women may be at higher risk of HPV vaccine failure.

Study details

Researchers reported results from 279 HIV-positive women and girls from whom data had been collected for about two years after vaccination with Gardasil. Their average profile upon entering the study was as follows:

• age – half of the participants were between the ages of 13 to 39, and the other half were between the ages of 39 and 66
• main ethno-racial groups: black – 42%, white – 36%, Indigenous – 14%, Asian – 5%
• duration of HIV infection – eight years
• CD4+ cell count – 500 cells/mm³; lowest-ever (nadir) CD4+ count – 230 cells/mm³
• proportion on ART with a viral load less than 50 copies/mL – 69%
• proportion who received all three doses of the vaccine – 95%

The researchers studied the protection afforded by Gardasil against new infections with HPV strains 6, 11, 16 and 18.

Results

The vaccine was safe and generally caused the production of high levels of antibodies against the four strains of HPV in the vaccine.

Biopsies showed that no women developed confirmed pre-cancers of the cervix caused by HPV strains 6, 11, 16 and 18.

Vaccine failures

The vaccine failed in eight women; four of these women developed genital warts and four others developed persistent infection caused by HPV 18. Although there were not sufficient cases of vaccine failure to draw statistically meaningful conclusions, the researchers noted the following:

• Women who experienced HPV vaccine failure tended to have lower CD4+ counts (333 cells/mm³) at the start of the study than women who did not experience vaccine failure (515 cells/mm³).
• The lowest-ever CD4+ cell count that women had experienced prior to initiating ART was lower (37 cells/mm³) among women with HPV vaccine failure compared to women who did not experience vaccine failure (240 cells/mm³).

Although some HIV-positive women vaccinated in the present study developed persistent HPV infection, the rate of this problem was lower than seen in other studies with unvaccinated HIV-positive women. Therefore, the Canadian researchers concluded that “although protection [with Gardasil] is not as complete as that seen in women without HIV infection, an important benefit appears to be present.”

Bear in mind

• The study continues to confirm the medium-term safety of Gardasil.
• A majority of vaccinated women were protected from new cases of infection by HPV and related disease (warts, abnormal cervical cells).
• The researchers stated that “present and historical immune dysfunction [caused by HIV] may contribute to breakthrough HPV infection and disease.”
• Given the relatively low rate of vaccine failure, the researchers stated that HPV vaccination should continued to be offered to “a wide age range” of girls and women who are HIV positive. They also stated that in addition to vaccination against HPV, “regular cervical screening remains important” in this population.

—Sean R. Hosein

REFERENCES:

1. McClymont E, Lee M, Raboud J, et al. The efficacy of the quadrivalent human papillomavirus vaccine in girls and women living with human immunodeficiency virus. Clinical Infectious Diseases. 2019 Feb 15;68(5):788-794.
2. Money DM, Moses E, Blitz S, et al. HIV viral suppression results in higher antibody responses in HIV-positive women vaccinated with the quadrivalent human papillomavirus vaccine. Vaccine. 2016 Sep 14;34(40):4799-806.