HPV test alone – new recommendation for cervical cancer screening

Current recommendations suggest women aged 25–65 years should be periodically screened for cervical cancer. The standard way this is done is by a Pap smear or by cotesting with a Pap smear with a human papilloma virus (HPV) test.

New interim guidance written by a group of cervical cancer screening experts suggests that HPV screening alone is a sufficient alternative to current testing methods, which use a Pap smear or a Pap smear plus an HPV test. The group of experts is led by Warner Huh from the University of Alabama at Birmingham (AL, USA). The new guidance suggests that the HPV test should be used as the primary screen for cervical cancer or its precursors and the Pap smear would be used for follow-up tests if the HPV test is positive.

The new guidance came about as last April the US FDA approved the use of an HPV test for primary cervical cancer screening. The guidance is being published simultaneously in three journals, Gynecologic Oncology, Obstetrics & Gynecology and the Journal of Lower Genital Tract Disease. Also published in Gynecologic Oncology is the end-of-trial data of the Roche Diagnostics ATHENA HPV trial.

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 US cytology-based (i.e., Pap smears) cervical cancer screening methods.” The authors note that existing guidelines still recommend Pap smears alone or cotesting with a Pap smear plus an HPV test for cervical cancer screening. However, this guidance is from 2011 and predates more recent clinical studies of HPV testing that were analyzed in the paper.

A key benefit of HPV testing is the lower rate of false-negative results: for women who receive a negative HPV test result from their primary screening there is 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.

The guidance states: “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 US.”

Huh also stated: “The scientific evidence clearly demonstrates that primary HPV testing outperforms cytology or Pap as a screening test. 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.”

The guidance also addresses four other questions that clinicians may have: “How should one manage a positive HPV result?”, “What is the optimal interval for primary HPV screening?”, “At what age should one initiate primary HPV screening?” and “How does primary HPV screening performance compare with cotesting?”

For the patient, the experience of getting an HPV test will be the same as getting a Pap smear, the difference is in how the sample is screened: with a Pap smear a technician examines the sample for abnormal cells but with an HPV test the sample is placed into a machine that detects HPV DNA.

There are still a number of questions and concerns facing HPV testing as it enters clinical practice. First, clinicians do need to be aware that false-negative results will still occur. Second, there are currently four commercially available HPV tests but only one is FDA approved for use for primary testing, and so clinicians should be aware of using tests that lack specific primary HPV screening indication. Third, comparative–effectiveness studies are required “that consider projected lifetime number of screening tests, colposcopies and follow-up visits,” as well as direct cost comparisons between primary HPV testing versus Pap smears and cotesting.

The guidance also noted that these updates apply to women who are regularly tested for cervical cancer but that there is a continuing need to identify women who are under- or un-screened.

Sources: 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 doi:10.1016/j.ygyno.2014.12.022 (2015) (Epub ahead of print); Huh WK, Ault KA, Chelmow D et al. Use of Primary High-Risk Human Papillomavirus Testing for Cervical Cancer Screening: Interim Clinical Guidance. Obstet Gynecol. (2015) (Epub ahead of print); Huh WK, Ault KA, Chelmow D et al. Use of Primary High-Risk Human Papillomavirus Testing for Cervical Cancer Screening: Interim Clinical Guidance. J. Low Genit. Tract. Dis. (2015) (Epub ahead of print); Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol. Oncol. doi:10.1016/j.ygyno.2014.11.076 (2015) (Epub ahead of print); University of Alamabama at Birmingham, Press release