HPV screening: Option to cytology-based options

EXECUTIVE SUMMARY

Primary human papillomavirus (HPV) screening can be considered as an alternative to current U.S. cytology-based cervical cancer screening methods, according to new interim guidance from two leading medical societies.

• Primary HPV testing can be considered for women starting at age 25. Women younger than age 25 should continue to follow current guidelines that recommend cytology alone beginning at age 21.

• Women with a negative primary HPV test result don’t need to be retested again for three years. This screening interval is the same one recommended under current guidelines for a normal cytology test result.

• An HPV test that reads positive for HPV 16 and 18 should be followed with colposcopy. A test that is positive for HPV types other than 16 and 18 should be followed by reflex cytology testing.

Primary human papillomavirus (HPV) screening can be considered as an alternative to current U.S. cytology-based cervical cancer screening methods, according to new interim guidance from the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology.¹

The interim guidance recommends:

• Primary HPV testing can be considered for women starting at age 25.

• Women younger than age 25 should continue to follow current guidelines that recommend cytology alone beginning at age 21.

• Women with a negative primary HPV test result should not be retested again for three years. This screening interval is the same one recommended under current guidelines for a normal cytology test result.

• An HPV test that reads positive for HPV 16 and 18, two types associated with a higher risk of future disease, should be followed with colposcopy, a test that allows the cervix to be examined under illumination and magnification.

• A test that is positive for HPV types other than 16 and 18 should be followed by reflex cytology testing.¹

The two groups reviewed 11 studies, the latest including end-of-trial data from the ATHENA HPV trial by Roche Diagnostics in Pleasanton, CA. Findings from this study, which enrolled more than 47,000 women in a longitudinal, three-year study of Roche’s cobas HPV Test, indicate that primary HPV screening is an effective screening strategy in women 25 years and older.² The Food and Drug Administration (FDA) approved the cobas test as a first-line primary screening test for cervical cancer in women ages 25 and older in April 2014.

There are four commercially available HPV tests in the United States: Hybrid Capture 2 from Qiagen, Gaithersburg, MD; CLART HPV2 Assay from Genomica, Madrid, Spain; APTIMA HPV Test from Hologic/Gen-Probe, San Diego; and the cobas HPV Test. The cobas test is the only test that has regulatory approval for primary HPV screening.

How important is it that clinicians use the approved test for primary screening in light of the recently published guidance and clinical data? “Very important,” says Warner Huh, MD, director of gynecologic oncology at the University of Alabama at Birmingham and a co-author of the interim report. “We don’t know what the performance of these other assays are in the setting of primary HPV screening and one of them, Qiagen, does not offer genotyping results, which is important for the algorithm in our guidance document,” says Huh. “Also, since this is a new form of screening, an FDA-approved test should be used specifically for this indication.”

How are the two societies getting out the word about the new interim guidance? According to Herschel Lawson, MD, chief medical officer of the American Society for Colposcopy and Cervical Pathology, a variety of methods is being used, including social media, press mentions, email, inclusion in Society-sponsored continuing medication education course materials, and information on the society’s website (http://www.asccp.org). Online webinars will be available soon without charge and with continuing education credit available, Lawson states. Lectures at a variety of scientific and clinical meetings are planned as well.

In 2012, oncology, pathology, and obstetrical/gynecological societies issued guidance recommending cytology every three years, or cytology plus HPV cotesting every five years, for women ages 30-64 with negative screening results, observes Andrew Kaunitz, MD, University of Florida Research Foundation professor and associate chairman of the Department of Obstetrics and Gynecology at the University of Florida College of Medicine — Jacksonville. For women ages 21 through 29, the guidelines recommend a Pap test every three years, with an HPV test only if the Pap is abnormal. Screening is not recommended for women younger than age 21.

According to Providing Quality Family Planning Services — Recommendations of CDC and the U.S. Office of Population Affairs, providers should offer cervical cancer screening to clients receiving related preventive health services. This guidance states to screen women ages 21-65 with cervical cytology (Pap smear) every three years, or for women ages 30-65, screening with a combination of cytology and HPV testing every five years.3 The recommendation acknowledges that screening women ages 21-65 every three years with cytology provides a reasonable balance between benefits and harm. HPV testing combined with cytology every five years in women ages 30-65 offers a comparable balance of benefits and harm, and it provides a reasonable alternative for women in this age group who would prefer to extend the screening interval.³

Kaunitz points to a recently published commentary that raises concerns that extending the cotesting screening interval from three to five years increases the number of women who will be diagnosed with and die from cervical cancer.⁴ A model used in the current United States Preventive Services Task Force estimates that among 1,000 women compliant with screening, increasing the interval results in an additional 2.71 and 0.61 women being diagnosed with, and dying from cervical cancer, respectively.⁵

“It can be perplexing for clinicians and our patients when guidelines change,” says Kaunitz. “In aggregate, however, these new publications suggest it is time to reconsider the five-year interval.”

Results of a newly released survey conducted by the National Association of Nurse Practitioners in Women’s Health and HealthyWomen, an independent women’s information source in Red Bank, NJ, suggest that women and their healthcare providers are resistant to change when it comes to revising cervical cancer screening protocols. The survey recorded information from more than 2,000 women and 750 healthcare providers nationwide.⁶ (Go to http://bit.ly/1ErTEfh for more information on survey results.)

Findings of the survey suggest women and providers favor routine cervical cancer screening and advocate continued use of the Pap test. More than 90% (91%) of healthcare providers say they believe the Pap test should remain part of frontline screening for the foreseeable future; 90% of women surveyed said they believe that the Pap test is important to their overall health and well-being.

Co-testing with the HPV test has been widely adopted by healthcare providers, particularly among nurse practitioners and obstetrician/gynecologists; 83% say it adds value to their patients’ health. About three-quarters (74%) of healthcare providers indicate that most of their patients would be most comfortable receiving both Pap and HPV tests. Twelve percent of healthcare providers noted their patients would be most comfortable with Pap test alone, with 2% indicating HPV test alone. Most healthcare providers said they prefer to see their patients every 1-3 years for cervical cancer screening; 76% of women said they are screened every one to three years.

“The data in this survey show that women and their healthcare providers truly value regular cervical cancer screening and are reluctant to change how often tests that we know to be successful are used,” said Beth Battaglino, RN, president and chief executive officer of HealthyWomen in a statement accompanying the survey findings. “Women should have these important conversations about cervical cancer screening with their healthcare providers to determine the best approach for their individual health needs.”

REFERENCES

1. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance. Gynecol Oncol 2015; doi: 10.1016/j.ygyno.2014.12.022.
2. Monsonego J, Cox JT, Behrens C, et al. Prevalence of high-risk human papilloma virus genotypes and associated risk of cervical precancerous lesions in a large U.S. screening population: Data from the ATHENA trial. Gynecol Oncol 2015; doi:10.1016/j.ygyno.2015.01.551.
3. Gavin L, Moskosky S, Carter M, et al. Centers for Disease Control and Prevention (CDC). Providing quality family planning services: Recommendations of CDC and the U.S. Office of Population Affairs. MMWR 2014; 63(RR-04):1-54.
4. Kinney W, Wright TC, Dinkelspiel HE, et al. Increased cervical cancer risk associated with screening at longer intervals. Obstet Gynecol 2015; 125(2):311-315.
5. Kulasingam SL, Havrilesky LJ, Ghebre R, et al. Screening for cervical cancer: A modeling study for the US Preventive Services Task Force. J Low Genit Tract Dis 2013; 17:193-202.
6. National Association of Nurse Practitioners in Women’s Health and HealthyWomen. Cervical Cancer Today: A National Survey of Attitudes and Behaviors. Washington DC, Red Bank, NJ; 2015.