By Amy Lane, Scientist
As Cervical Health Awareness Month comes to a close, it is a good time to review the state of cervical cancer, what you can do personally, and what is happening in drug development.
Cervical cancer is most often caused by the human papillomavirus (HPV) and generally develops slowly with abnormal cells eventually becoming malignant in the tissue of the cervix. This transformation from healthy to abnormal to malignant cells takes time to develop1,2. In the United States, the National Cancer Institute (NCI) estimated there would be 13,240 new cervical cancer cases and 4,170 deaths3.
Prevention of cervical cancer is ideal, and from 2006-2015, new cases of cervical cancer had stabilized and death rates were declining at 0.7% annually3. Much of this is due to the availability of HPV vaccines. There are seven types out of the more than 100 kinds of HPV that are responsible for the majority of cervical cancers as well as two indicated in genital warts. In 2006, the FDA approved the HPV vaccine, Gardasil®, to prevent four of the nine types damaging to cervical health. The vaccine was available to females 9 – 26 years old and according to the CDC cut rates of infection by 64% in American teenagers and 34% in women in their early 20s6. In December, 2014, Gardasil-9®, a vaccine against 9 types of HPV was approved to provide further protection.
According to the NCI, the age group most commonly diagnosed with cervical cancer are women 35-44 (23.6%) years old3. In October of 2018, the FDA expanded the ages approved for the HPV vaccine to include ages 27 – 45 years. While it is too soon to determine the effect of extending vaccine protection to the most often diagnosed age group, it provides another route to continue the decline of cervical cancer incidence.
Unfortunately, the HPV vaccine is not 100% effective, therefore, early detection remains important. Regular testing by a pap test (or pap smear), can identify abnormal changes in cervical cells indicating follow-up testing. Follow-ups may include another pap smear, an HPV test or a cervical biopsy. Due to the slow development, pap smears are recommended every three years for women between the ages of 21 and 65 years with a healthy cervical history4. Women 30 years and older may select a pap smear every five years in combination with HPV testing5. When identified early there are often positive outcomes, 5-year relative survival rates are 91.5% in women diagnosed with localized cervical cancer3.
Even with positive outcomes in localized cases, the 5-year survival rate is 66.2% leaving a need for continued improvement in late-stage and recurrent cancer treatments3. In addition to chemotherapy, early treatments included single-agent immunotherapy drugs intended to remove the barrier that cancer cells build to block immune response. Alone, these drugs have shown activity in 15% to 25% of patients, leaving ample space for improvement7.
Currently, combined therapies are being investigated, including two studies in advanced, recurrent cervical cancer. One pairs an immunotherapy drug (atezolizumab) with an antiangiogenic agent (bevacizumab). Preclinical data suggest the use of the antiangiogenic agent may improve immunotherapy efficacy8. The other combines two immunotherapy drugs (durvalumab and tremelimumab) with radiotherapy. Researchers are investigating the potential for radiation to improve the immune response9. Both studies have anticipated completion dates in the next one to two years.
Progress for improving cervical cancer outcomes has increased through prevention opportunities with vaccine availability and with continued diligence in regular appointments allowing early detection and treatment. Today efforts continue in drug development studies for late-stage and recurrent treatments to continue to discover more efficient and effective pathways to improve outcomes as we move forward with those still fighting.
- Cervical Cancer Treatment (PDQ®)-Patient Version. National Cancer Institute Website. Available at: https://www.cancer.gov/types/cervical/patient/cervical-treatment-pdq#link/_117. Accessed 17 January 2019.
- Improving Your Odds for Cervical Health. U.S> food & Drug Administration website. Available at: https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm383757.htm. Accessed 21 January 2019.
- Cancer Stat Facts: Cervical Cancer. National Cancer Institute, Surveillance, Epidemiology and End Results Program. Available at: https://seer.cancer.gov/statfacts/html/cervix.html. Accessed 15 January 2019.
- Cervical Cancer Screening Guidelines for Average-Risk women. Available at: https://www.cdc.gov/cancer/cervical/pdf/guidelines.pdf. Accessed 21 January 2019.
- Pap Smear. Mayo Clinic website. Available at: https://www.mayoclinic.org/tests-procedures/pap-smear/about/pac-20394841. Accessed 21 January 2019.
- Markowitz LE, Liu G, Hariri S, Steinau M, Dunne EF, Unger ER. Prevalence of HPV After Introduction of the Vaccination Program in the United States. American academy of Pediatrics. 2016. Available at: http://pediatrics.aappublications.org/content/137/3/e20151968. Accessed 21 January 2019.
- New Clinical Trials Test Immunotherapy for Cervical Cancer. Insight from Dana Farber Cancer Institute. Available at: https://blog.dana-farber.org/insight/2018/03/new-clinical-trials-test-immunotherapy-cervical-cancer/. Accessed 22 January 2019.
- Phase 1 / 2 Study of AGEN2034 in Advanced Tumors and Cervical Cancer. ClinicalTrials.gov website. Available at: https://clinicaltrials.gov/ct2/show/study/NCT03104699#contacts. Accessed 22 January 2019.
- Durvalumab, Tremelimumab + Radiotherapy in Gynecologic Cancer. ClinicalTrials.gov website. Available at: https://clinicaltrials.gov/ct2/show/NCT03277482. Accessed 22 January 2019.