By Rebecca Bowers

EXECUTIVE SUMMARY

Researchers are moving ahead with studies of a potential immunotherapeutic, nonsurgical approach to treating cervical intraepithelial neoplasia caused by human papillomavirus infection (HPV).

  • Cervical cancer is caused primarily by persistent infection with high-risk HPV in which individuals fail to mount a sufficient immune response against the virus.
  • Prophylactic HPV vaccines are used to generate antibodies to neutralize viral particles, while therapeutic HPV vaccines stimulate cell-mediated immune responses to target and kill infected cells.
  • Current treatment for cervical intraepithelial neoplasia may lead to scarring and a shortened cervix, which can cause problems during childbirth and lead to increased risk of cesarean section.

Researchers are moving ahead with studies of a potential immunotherapeutic, nonsurgical approach to treating cervical intraepithelial neoplasia (CIN) caused by human papillomavirus (HPV) infection.1

The third most common cancer in women, cervical cancer is caused primarily by persistent infection with high-risk HPV, in which individuals fail to mount a sufficient immune response to the virus.2 There are very few products trying to cure women who already have an HPV infection, notes Diane Harper, MD, MPH, MS, professor of family medicine and obstetrics and gynecology at Michigan Medicine. Prophylactic HPV vaccines are used to generate antibodies to neutralize viral particles, while therapeutic HPV vaccines stimulate cell-mediated immune responses to target and kill infected cells. Clinicians are familiar with prophylactic HPV vaccines. Routine immunization is recommended for girls and boys at age 11 or 12, and the series can be started at age 9. Immunization also is recommended through age 26 for females and through age 21 for males. Males 22-26 years of age also may be immunized.3 Although the Food and Drug Administration has approved the use of the nine-valent HPV vaccine in women and men ages 27-45, the Advisory Committee on Immunization Practices is reviewing further information and moving toward a potential vote on the matter.

In results of a recent study conducted by Harper and associates, women who received a potential vaccine, known as tipapkinogen sovacivec, were more than twice as likely as those who received placebo to see their CIN eliminated regardless of the type of HPV infection.

“It’s very exciting. This is the first time we’ve seen something with this success rate that is relatively easy to implement,” said Harper in a press statement.

Focus on Research

In the current study, scientists enrolled 192 women diagnosed with CIN2 or CIN3; 129 were selected randomly to receive the vaccine, while 63 were assigned a placebo. Study participants received a total of three shots in the thigh, which were given once per week for three weeks. After six months, participants received treatment with standard surgical procedures for CIN 2/3, with examination performed on the removed tissue.

Complete resolution was significantly higher in the vaccine group than in the placebo group for CIN 2/3, regardless of which of the 13 high-risk HPV types was assayed (24% vs. 10%, P < 0.05). Figures also were higher for complete resolution for women with CIN 3, regardless of high-risk HPV type (21% vs. 0%, P < 0.01). Researchers followed the participants for another two and a half years after surgery, with results indicating that more women in the vaccine group remained completely clear of HPV. Scientists noted that the vaccine was tolerated well, with injection site reactions being the most common reported adverse events.1

Stopping the Infection

High-grade cervical intraepithelial neoplasia (CIN 3) has an incidence of about one to two per 10 females with low-grade CIN. Without treatment, progression to cervical cancer occurs in about one-third of cases.4 Current treatment for CIN 2 and 3 may include laser therapy, cryotherapy, loop electrosurgical procedure (LEEP), or cone biopsy to remove or destroy the abnormal tissue. Such treatments may lead to scarring and a shortened cervix, which can cause problems
during childbirth and lead to increased risk of cesarean section. In addition, women who undergo this procedure have a very high risk of developing cervical cancer over the next 20 years if they do not continue to be screened.

“The surgical procedure removes all the tissue that is headed towards cancer, but it doesn’t remove all the HPV,” says Harper, who also serves as a member of the University of Michigan Rogel Cancer Center and senior associate director of the Michigan Institute for Clinical and Health Research.

In the current study, researchers found that the tipapkinogen sovacivec vaccine not only eliminated the lesions, but also eliminated the HPV infection.

REFERENCES

  1. Harper DM, Nieminen P, Donders G, et al. The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up. Gynecol Oncol 2019; doi:10.1016/j.ygyno.2019.03.250. [Epub ahead of print].
  2. Vici P, Mariani L, Pizzuti L, et al. Immunologic treatments for precancerous lesions and uterine cervical cancer. J Exp Clin Cancer Res 2014;33:29.
  3. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination — updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2016;65:1405-1408.
  4. Trottier H, Franco EL. The epidemiology of genital human papillomavirus infection. Vaccine 2006;24(Suppl 1):S1-S15.