New recommendation for cervical cancer screening, using HPV test alone

January 8, 2015 by Traci Bratton, University of Alabama at Birmingham

About 80 million U.S. women ages 25 to 65—or 1.2 million women across Alabama—should be screened periodically by their health care providers for cervical cancer. At present, the standard way to do that is a Pap smear alone, or co-testing using both a Pap smear and a human papillomavirus (HPV) test.

Today, the clinicians who care for those women are getting new interim guidance about the health advantages of instead using the HPV alone as the primary screen to find or its precursors. Under the new guidance, the Pap smear, which dates back more than 80 years, would still be used for follow-up tests if an HPV test is positive. The Pap smear will still be used for primary of women under age 25.

The need for guidance about using the HPV test was triggered last April when the FDA approved one existing HPV test for use in primary cervical cancer screening. Today's guidance, written by a group of cervical cancer screening experts led by University of Alabama at Birmingham gynecologic oncologist Warner Huh, M.D., is being published simultaneously in the journals Gynecologic Oncology, Obstetrics & Gynecology, and the Journal of Lower Genital Tract Disease under the title "Use of Primary High Risk Human Papillomavirus Testing for Cervical Cancer Screening: Interim Clinical Guidance." Also published today in Gynecologic Oncology is the end-of-trial data of the Roche Diagnostics ATHENA HPV trial that enrolled more than 47,000 women in a longitudinal, three-year study of Roche's HPV test.

"Although FDA approval is critically important for introducing a new screening test or algorithm, providers ultimately rely on guidance or guidelines to help them make the best decisions for their patients and want to understand advantages, disadvantages and unknowns associated with a new screening approach," said Huh, who is a senior scientist for the UAB Comprehensive Cancer Center, Director of the UAB Division of Gynecologic Oncology, and is also a board member for both the American Society for Colposcopy and Cervical Pathology and the Society of Gynecologic Oncology.

Major conclusions

The two major conclusions of the interim guidance panel are:

  • "Because of equivalent or superior effectiveness," the paper says, "primary HPV screening can be considered as an alternative to current U.S. cytology-based (i.e., Pap smears) cervical cancer screening methods." The authors note that the existing, previously published guidelines still recommend Pap smears alone, or co-testing with a Pap smear and an HPV test, for cervical cancer screening. However, those guidelines from 2011 predate more recent clinical studies of HPV testing that were analyzed in today's paper.
  • Women who have a negative HPV test result from their primary screening have a greater reassurance of a very low risk for a future cervical cancer precursor lesion, as compared to women who have a negative Pap smear test in their primary screening. This lower rate of false negative results is a key benefit of the HPV screening.

Overall, the panel said, "While there continue to be numerous practical and research questions, primary HPV testing has the potential to further reduce morbidity and mortality of cervical cancer in the U.S. However, what is most important is that women need to be screened with any strategy, as many women in the U.S. with cervical cancer are either unscreened or underscreened."

"The scientific evidence clearly demonstrates that primary HPV testing outperforms cytology or Pap as a screening test," said Huh. "This has been confirmed from numerous European and Canadian studies as well as the ATHENA trial. There are going to be fewer false negatives with HPV, and arguably, we have been using a less sensitive test for screening for a while now."

Huh added, "Pap smears miss a fair number of adenocarcinomas. We don't want a test that will miss disease."

From the patient's point of view, the experience of getting an HPV test will be the same as getting a Pap smear. The difference is how the sample is then screened: Instead of a technician looking for abnormal cells (Pap), the HPV sample is put into an automated machine to detect HPV DNA.

Other questions

The guidance also addresses four other questions that clinicians may have.

1. How should one manage a positive HPV result?

While data are still limited, the study group suggested a flowchart algorithm, as follows. If a woman is positive for HPV genotypes 16 or 18, which convey the greatest risk of developing cervical cancer precursor lesions in the next three years, she should be referred for a colposcopy (an illuminated, magnified examination of the cervix and other genital tissue for premalignant or malignant lesions). If a woman is positive for the 12 other lower-risk HPV genotypes, she should get a Pap smear; and if that Pap smear is also positive, she should then get a colposcopy. If her follow-up Pap smear is negative, she should be retested with another Pap smear in 12 months. This algorithm "achieves a reasonable balance of disease detection with the number of screening tests and colposcopies required to achieve that detection," the panel wrote.

2. What is the optimal interval for primary HPV screening?

Data are limited for determining the optimal screening interval, but the interval should be no sooner than every three years. There is no need to screen more frequently than every three years, since the cumulative occurrence of a cervical cancer precursor lesion called a CIN3+ during the three years after a negative HPV test was less than 1 percent.

3. At what age should one initiate primary HPV screening?

It should not begin before age 25. The study panel noted that about 30 percent of the CIN3+ cervical cancer precursor lesions in the ATHENA study occurred in women ages 25 to 29. A majority of women ages 25 to 29 who have CIN3+ have normal Pap smears. Another 37 percent of the CIN3+ lesions in the ATHENA study were found in women 30 to 39 years old. The panel did have some concerns that starting at age 25—even though it increases detection of disease—would lead to too many colposcopies in women whose progression to cancer is uncommon.

4. How does primary HPV screening performance compare with co-testing?

The panel said that most of the reassurance of safety provided by a co-test (a Pap smear together with an HPV test) derives from the HPV test. Analysis of about 1 million women screened at Kaiser Permanente Northern California suggests that HPV screening with a three-year interval between negative tests is at least as effective as co-testing every five years. However, co-testing is still an appropriate and recommended screening strategy, Huh noted.

The future

As the new advance of primary HPV screening enters into clinical practice, there will be a number of additional questions and concerns, the panel said. First, clinicians need to be aware that false negative tests will still occur—that is, some women will still develop invasive cancer, even though their HPV tests were negative.

Second, at present there are four commercially available, FDA-approved HPV tests; but only one of them is FDA-approved for primary screening. While the panel hopes that there will be other tests that will be rigorously validated and approved for primary screening sometime in the near future, clinicians should not use a test that lacks a specific primary HPV screening indication.

Third, the panel noted a need for comparative effectiveness studies "that consider projected lifetime number of screening tests, colposcopies and follow-up visits," as well as direct cost comparisons between primary HPV testing vs. Pap smears and co-testing. Further information is also needed about the cancer risks if the interval between HPV tests is extended from three years to five years.

While today's guidance applies to women who receive regular screening for cervical cancer, the panel also noted the continuing need to identify who are still unscreened or underscreened.

"One major aspect of cervical cancer prevention that needs to be discussed in light of screening is HPV vaccination," said Huh. "Particularly with the recent FDA approval of the new 9-valent HPV vaccine and evidence that the vaccine decreases HPV and disease prevalence, I have concerns that this will put an additional strain on the performance of cytology (i.e., Pap smear). We will need to look at other tests like HPV as a more appropriate screening test as disease rates decrease over time."

Explore further: What's the best test for cervical cancer? Pap, HPV or both?

Related Stories

What's the best test for cervical cancer? Pap, HPV or both?

June 9, 2014
Should U.S. women be screened for cervical cancer with Pap tests, HPV tests or both? According to researchers from Boston University School of Medicine (BUSM) and Boston Medical Center (BMC) while the merits of screening ...

A negative HPV test may predict lower cervical cancer risk than a negative Pap

July 19, 2014
In the US, cotesting for human papilloma virus (HPV) and Pap testing for cervical cancer every 5 years for women aged 30-65 years is now recommended. However, HPV testing alone may provide better reassurance against cervical ...

FDA experts debate timing of pap test

March 12, 2014
(HealthDay)—The Pap test has been a routine gynecological procedure for generations of American women. But on Wednesday, a Food and Drug Administration advisory panel is considering whether to delay the Pap test and use ...

Female doctors twice as likely to screen low-risk women for cervical cancer with HPV test

November 7, 2013
For low-risk women, the likelihood that they get tested for the infection that causes cervical cancer (human papillomavirus or HPV) may depend on what clinic they visit, their doctor's status and whether their provider is ...

Urine HPV test could offer non-invasive alternative to conventional smear, improve screening uptake

September 16, 2014
Human papillomavirus (HPV) is one of the most common sexually transmitted infections. Up to 80% of sexually active women are infected at some point in their lives and infection with specific "high risk" strains of HPV has ...

Longer screening intervals possible with HPV-based tests

January 21, 2014
A new study from Karolinska Institutet in Sweden finds that testing for human papilloma virus (HPV) allows for longer time between screening tests when compared to cytology-based testing. The study is published in the scientific ...

Recommended for you

Stem cell vaccine immunizes lab mice against multiple cancers

February 15, 2018
Stanford University researchers report that injecting mice with inactivated induced pluripotent stem cells (iPSCs) launched a strong immune response against breast, lung, and skin cancers. The vaccine also prevented relapses ...

Induced pluripotent stem cells could serve as cancer vaccine, researchers say

February 15, 2018
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine. Outside the body, they can be coaxed to become many different types of cells and tissues that can help repair damage due to trauma or ...

Team paves the way to the use of immunotherapy to treat aggressive colon tumors

February 15, 2018
In a short space of time, immunotherapy against cancer cells has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind ...

Can our genes help predict how women respond to ovarian cancer treatment?

February 15, 2018
Research has identified gene variants that play a significant role in how women with ovarian cancer process chemotherapy.

First comparison of common breast cancer tests finds varied accuracy of predictions

February 15, 2018
Commercially-available prognostic breast cancer tests show significant variation in their abilities to predict disease recurrence, according to a study led by Queen Mary University of London of nearly 800 postmenopausal women.

Catching up to brain cancer: Researchers develop accurate model of how aggressive cancer cells move and spread

February 15, 2018
A brief chat at a Faculty Senate meeting put two University of Delaware researchers onto an idea that could be of great value to cancer researchers.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.