Screening for HPV Infection Alone More Accurate Than Pap Test in the Detection of Cervical Cancer, Especially in Younger Women

Interim clinical guidance and end of study results from the ATHENA study

Screening for human papillomavirus (HPV) infection alone gives more accurate results than Pap testing for cervical cancer, according to the authors of two papers published in the journal Gynecologic Oncology. HPV infection causes almost all cervical cancer, and it is estimated that more than half of sexually active people are infected with HPV at some point in their lives. Now new research has shown that in many cases, an HPV test alone can be used for cervical cancer screening instead of a Pap or co-testing with both, an HPV and a Pap test.

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or co-testing (cytology in combination with high-risk HPV testing). These guidelines also addressed the use of high-risk HPV testing alone as a primary screening approach, which was not recommended for use at that time.

There is now a growing body of evidence for screening with primary high-risk HPV testing, including a prospective USA-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary high-risk HPV screening.

In the paper published in Gynecologic Oncology, Dr Warner Huh, from the Department of Gynecologic Oncology, University of Alabama, Birmingham, USA and colleagues, set out the findings of a panel convened to provide guidance on using HPV as the first-line primary screening test. The panel addressed questions related to the safety and effectiveness of HPV testing for primary screening and whether it could be considered as an alternative to the screening methods currently in use in the USA.

The panel was convened because of an application to the Food and Drug Administration (FDA) for an existing HPV test to be used for primary HPV cervical cancer screening. The guidance was based on a literature review and also on review of data from the ATHENA study which was conducted to support the primary screening application to the FDA.

The panel found that, in patients aged 25 years and upwards, primary HPV testing performed better than a Pap alone, and the panel recommended that such tests should be carried out no sooner than every three years. “This is an important advance in cervical cancer screening because it offers a better reassurance of low cancer risk compared to Pap screening, which is also carried out at three year intervals," according to Dr Huh.

Infection with just two HPV genotypes, 16 and 18, is responsible for about 70% of all invasive cervical cancers worldwide. The panel recommended that patients testing positive for either of these two high risk genotypes should have immediate colposcopy.  Women with one of the 12 other HPV genotypes can be followed-up in 12 months with repeat testing with both the HPV test and a Pap.

"We believe that there is still considerable confusion over the three current screening options, and the intervals at which they should be performed. We hope that our deliberations will go some way towards reducing this uncertainty. However, I would still like to see more data from the US, and evidence from other countries using primary HPV screening such as Australia and The Netherlands. But in the absence of data to the contrary, we believe that primary HPV testing has potential to further reduce cervical cancer in the US," Dr Huh said.

The second paper reveals end of study results of the ATHENA trial which evaluated safety and effectiveness of HPV primary screening as an alternative to Pap in women of 25 years and older. In total 42,209 women in this age group were enrolled into the trial and had both Pap and HPV testing. Those with abnormal Pap test results and those who were HPV positive were referred for colposcopy.

The researchers found that HPV primary screening was as effective in women aged 25 years and over when compared to Pap alone for women 25 and 29 and co-testing for those aged 30 and over. “However, HPV screening alone requires only one test, and this is important for many women who may not be able to afford the cost of two tests," said Dr Thomas Wright, a Professor Emeritus of Pathology and Cell Biology at Columbia University, New York, USA.

To determine the impact of starting HPV screening at different ages, the researchers compared the prevalence of HPV positivity and Pap abnormalities as well as the three year detection rate of high-grade cervical disease by age group. They found that although HPV positivity was almost twice as high in women aged 25-29 as it was in women aged 30-39, HPV testing identified about twice as many high-grade cervical disease cases in women aged 25-29 than did the Pap.

"When Pap screening is used in this age group, the women with missed high-grade cervical disease are told to return in three years for repeat screening and some are likely to develop invasive cervical cancer", according to Dr Wright.

"Our results, from the first prospective US study to evaluate the performance of HPV primary screening, have shown clearly that this new screening approach should be considered as an option for women 25 years and older", Dr Wright said. However, he added that the recent FDA approval for HPV primary screening is limited to a single commercially available HPV test and to only one of the two widely utilised liquid-based Pap tests. "In order to facilitate the widespread adoption of this safe and effective method of screening, it would be advantageous to have additional HPV tests and the other liquid-based Pap tests approved. We hope that our research will help reduce morbidity and mortality from cervical cancer worldwide," he said.

References

Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance, Gynecologic Oncology 2015; Published online January 7. DOI: http://dx.doi.org/10.1016/j.ygyno.2014.12.022

Wright TC, Stoler MH, Behrens CM, et al. Primary cervical cancer screening with human papillomavirus: End of study results from the ATHENA study using HPV as the first-line screening test. Gynecologic Oncology 2015; Published online January. DOI: http://dx.doi.org/10.1016/j.ygyno.2014.11.076