By Rebecca Bowers

EXECUTIVE SUMMARY

In a large, randomized clinical trial that compared primary HPV testing alone vs. Pap test for cervical screening, results suggest that primary HPV testing can pick up precancerous lesions sooner and with better accuracy than the Pap test.

  • Data also indicate that women who tested negative for HPV were less likely than women screened by Pap tests to have cervical precancer after four years.
  • The U.S. Preventive Services Task Force issued draft guidance in 2017 that states for women of average risk who are 30-65 years of age, testing for cervical cancer may be done using cervical cytology alone every three years or using HPV testing.

In a large, randomized clinical trial that compared primary human papillomavirus (HPV) testing alone vs. Pap test for cervical screening, results suggest that primary HPV testing can pick up precancerous lesions sooner and with better accuracy than the Pap test. Women who tested negative for HPV were less likely than women screened by Pap tests to have cervical precancer after four years, data indicate.1

The Canadian study is the first clinical trial comparing the effectiveness of HPV testing vs. Pap testing. It was headed by scientists from the University of British Columbia, British Columbia Cancer, and the British Columbia Centre for Disease Control.

“Our results, by demonstrating the increased accuracy of HPV screening, show that the HPV
test will detect pre-cancerous lesions sooner so they can be removed or destroyed before becoming cancerous,” says lead author Gina Ogilvie, MD, FCFP, professor in the University of British Columbia School of Population and Public Health and senior research advisor at the British Columbia Women’s Hospital & Health Centre.

When the Pap test was introduced some 50 years ago, it “dramatically” lowered the number of women who died from cervical cancer, Ogilvie noted in a press announcement accompanying the publication. The HPV test can move that number “much closer to zero,” she stated.

Review the Results

From 2008 to 2016, researchers recruited 19,009 women ages 25 to 65 from the Vancouver metro area and greater Victoria. Participants included women who had not received a Pap test during the prior 12 months, were not pregnant, and were not HIV-positive or taking immunosuppressive therapy. Participants also did not have a history of CIN2+ (cervical intraepithelial neoplasia II+) in the past five years, and had no history of invasive cervical cancer or hysterectomy.

Women enrolled in the study were randomly assigned to one of two arms: the intervention group, which received HPV testing alone, and the control group, which received liquid-based cytology testing. Those who received HPV testing alone and had negative results were called back at 48 months to exit the study with HPV and liquid-based cytology testing. For those who had liquid-based cytology and received negative results, researchers asked that they return at 24 months to have repeat testing using liquid-based cytology. If those results were negative at the 24-month screen, investigators asked the women to return at 48 months to exit the study and receive HPV and liquid-based cytology testing. If a woman tested positive in either arm of the study, and was later found to have precancerous cells, she was referred for treatment. The HPV test used in the study looked for HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68.

When the study concluded four years later, researchers found fewer of the remaining women in the HPV test group had precancerous cells, since the HPV test had been identifying more women for closer examination. As a result, women who were screened for HPV at the start were almost 60% less likely to have a precancerous lesion four years later, compared to those tested with Pap tests.1

“This study showed that the HPV test is reliable enough to give peace of mind to women who have tested negative, and that those results are good for at least four years,” said coauthor Dirk van Niekerk, MB, CHB, medical leader of British Columbia Cancer’s Cervix Screening Program and University of British Columbia clinical assistant professor of pathology and laboratory medicine, in a statement. “That means HPV testing could be done less frequently than Pap tests are currently done, and with more women getting treatment at the earliest possible opportunity.”

Check the Guidance

The U.S. Preventive Services Task Force (USPSTF) issued a draft guidance in 2017 stating that for women of average risk who are 30-65 years of age, testing for cervical cancer may be done using cervical cytology alone every three years or using HPV testing. Co-testing is not required any longer.2 The Task Force recommends that women ages 21-29 undergo cervical cancer screening every three years with cervical cytology alone. The task force recommends cervical cancer screening for women ages 30-65 either using cervical cytology alone every three years or using HPV testing alone every five years. (Contraceptive Technology Update reported on the guidance; see the December 2017 article, “Task Force Issues Cervical Cancer Screening Guidance: What Changes Can Clinicians Expect?” available at http://bit.ly/2ErPxud.)

The American College of Obstetricians and Gynecologists (ACOG) affirms its clinical guidance, recommending co-testing with cytology and HPV testing every five years as the preferred screening method for women ages 30-65, and using cytology alone every three years as an acceptable screening method.3 The USPSTF draft recommendations about routine screening for cervical cancer remain unchanged and are the same as the guidance from ACOG for women who are younger than 21 years of age, who are 21-29 years of age, or who are older than 65 years of age and have been screened adequately before. Both the Task Force and ACOG recommend against screening for cervical cancer for women who are younger than 21 years of age.

In women 21 to 65 years of age, regular screening lowers the cervical cancer rate significantly and decreases the number of deaths from cervical cancer.4 According to the USPSTF evidence search, the screening method that is most effective varies according to a woman’s age. In women who are 21-29 years of age, HPV infections may resolve on their own. In this group, the Pap test is most effective.5 HPV infections in women ages 30-65 are more likely to lead to cancer. In this group, the effective screening methods are either Pap tests or HPV tests, according to the evidence review.2 Costs of a Pap test for women who do not have health insurance range from $25 to $40, with cost of HPV screening estimated at $45 to $60.

While refinements are being made in how cervical cancer screening is performed, clinicians should remember that most cervical cancers continue to be diagnosed in women who have not received adequate screening, or who have received inappropriate care after abnormal screening results, notes Andrew Kaunitz, MD, University of Florida term professor and associate chairman of the Department of Obstetrics and Gynecology at the University of Florida College of Medicine-Jacksonville. Efforts must continue to be made to reach those not currently being screened, he notes.

HPV vaccination also holds promise in driving down cervical cancer rates. In a recent report from the Centers for Disease Control and Prevention, data indicate HPV vaccination rates are rising among teenagers in the United States. In 2016, 60% of teens ages 13-17 received one or more doses of the HPV vaccine, an increase of four percentage points from 2015.6 The vaccine protects against HPV, which can cause many types of cancer.

REFERENCES

  1. Ogilvie GS, van Niekerk D, Krajden M, et al. Effect of screening with primary cervical HPV testing vs cytology testing on high-grade cervical intraepithelial neoplasia at 48 months: The HPV FOCAL randomized clinical trial. JAMA 2018;320:43-52.
  2. U.S. Preventive Services Task Force. Draft Recommendation Statement: Cervical Cancer: Screening. Available at: https://bit.ly/2h73xLJ. Accessed July 20, 2018.
  3. American College of Obstetricians and Gynecologists, Committee on Practice Bulletins — Gynecology. Practice Bulletin No. 168: Cervical cancer screening and prevention. Obstet Gynecol 2016;128:e111-e130.
  4. Safaeian M, Solomon D, Castle PE. Cervical cancer prevention — cervical screening: Science in evolution. Obstet Gynecol Clin North Am 2007;34:739-760.
  5. Kotaniemi-Talonen L, Anttila A, Malila N, et al. Screening with a primary human papillomavirus test does not increase detection of cervical cancer and intraepithelial neoplasia 3. Eur J Cancer 2008;44:565-571.
  6. Walker TY, Elam-Evans LD, Singleton JA, et al. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years — United States, 2016. MMWR Morb Mortal Wkly Rep 2017;66:874-882.