Study Suggests HPV Test More Accurate Than Pap Smear for Cervical Cancer Screening

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During the first round of screening, a human papillomavirus (HPV) test detected more abnormal cells grade 3 or worse in the cervix than a Papanicolau (Pap) smear, resulting in a lower liklihood of abnormal cells grade 3 or worse at 48 months.

When it comes to cervical cancer screening, most women receive a cytology-based Papanicolau (Pap) smear, where cells are scraped from the back of the cervix. However, human papillomavirus (HPV)-based testing may be a more accurate way of testing for cervical cancer, new study results suggest.1

Despite the widespread use of cervical cancer screening with a Pap smear, it was estimated that approximately 12,820 women in the United States would develop, and 4210 would die, from cervical cancer in 2017. As over 99% of all cervical cancers are associated with HPV, testing for the infection has been touted as an alternate option for cervical cancer screening. Previous research has indicated that HPV testing alone or combined with a Pap smear is linked to increased detection of precancerous lesions in the first screening round, followed by a subsequent reduction in precancerous lesions.

However, major organizations, such as the American Society of Clinical Oncology, have called for clinical trials involving HPV testing alone for more than 1 round of screening to further inform the implementation of the screening.

To determine the efficacy of primary HPV testing alone, researchers conducted the 4-year HPV For Cervical Cancer (HPV FOCAL) screening trial of women age 25 to 65. Women were recruited from January 2008 through May 2012 and followed through December 2016.


A total of 19,009 women were randomized to receive either HPV testing (intervention group) or a Pap smear (control group). Women with negative Pap smear results received a second Pap smear after 24 months. After 48 months, both groups received HPV screening and a Pap smear.

Consistent with prior studies, more cases of abnormal cells in the cervix, known as cervical intraepithelial neoplasia (CIN), grade 3 or worse (CIN3+), were detected in the intervention group compared with the control group in the first round of screening. By 48 months, there were significantly fewer cases of CIN2+ and CIN3+ detected among all age groups in the intervention group.

The researchers observed that women who were HPV-negative at baseline were significantly less likely to have CIN2+ or CIN3+ at 48 months compared with those who had negative Pap smear results at baseline. “These results have demonstrated that primary HPV testing detects cervical neoplasia earlier and more accurately than cytology,” they wrote.

However, by the end of follow-up (72 months), incidence was similar across both groups.

The researchers also noted concerns over lower CIN2+ specificity with HPV testing, leading to higher screen positive rates and therefore more colonoscopies and biopsies, which could cause unintended harms for women and increased costs if the tests prove unnecessary.

Last fall, the United States Preventive Services Task Force recommended that women age 30 or older receive just 1 screening method—a Pap smear or an HPV test—instead of co-testing. Chris Zahn, MD, vice president of practice, American College of Obstetricians and Gynecologists, said in an email that studies like the HPV FOCAL trial can lead to a change in the guidelines.

According to Kathleen Schmeler, MD, gynecologic oncologist, University of Texas MD Anderson Cancer Center, even if guidelines do change for women age 30 and older, the Pap smear is still important for women age 21 to 29. Schmeler believes that the age group can’t rely on HPV testing because the majority will contract HPV at some point, and in many cases, it goes away on its own.

However, if the virus persists until their 30s, that’s when it becomes a problem. “If you tested everyone for HPV in their 20s, they are almost all going to be positive, but there’s going to be all of this intervention that’s not needed,” she said.


1. Ogilvie G, 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 [published online July 3, 2018]. JAMA. doi:10.1001/jama.2018.7464.