Is HPV testing ready to replace Pap testing as the first-line test for cervical cancer screening for women 25 and older? That was the question at this year’s John and Marney Mathers Lecture.
Warner K. Huh, MD, professor and division director of gynecologic oncology, senior scientist in the University of Alabama-Birmingham (UAB) Comprehensive Cancer Center, and Margaret Cameron Spain endowed chair in Obstetrics and Gynecology at the UAB School of Medicine, says yes. But George F. Sawaya, MD, professor of Obstetrics, Gynecology and Reproductive Sciences and Epidemiology & Biostatistics at the University of California, San Francisco, argued for a more cautious approach during the Sunday morning debate.
Dr. Huh said that HPV testing offered the most sensitivity and negative predictive value out of all the screening technologies. A negative HPV test gives long-term confidence that a lesion is not present.
He highlighted the Canadian Cervical Cancer Screening Trial study of 10,171 women ages 30-69 in Canada randomized to Pap or HPV. HPV had an estimated sensitivity of 94.6 percent, while Pap had a sensitivity of 55.4 percent. Pap also suffers from variations in lab performance.
“Keep in mind that cytology has never been subject to a randomized control trial, and if you actually submitted the test to the FDA today, what’s interesting is that it would probably be resoundingly rejected by the FDA because of it’s low sensitivity,” Dr. Huh said.
An aggregate of four European studies published in the Lancet in 2011 cited by Dr. Huh found that for all women who had a normal result on a Pap test, there was a rate of 7.5 instances of cervical cancer per 100,000 women a year. For women who were HPV-negative, the rate was 3.8 cervical cancers per 100,000. Women who were both HPV-negative and had a normal Pap test had 3.2 cervical cancers per 100,000.
“It’s an astounding difference over time. When you actually calculate it, it’s about a 60 percent risk reduction of cervical cancer over this time period,” he said.
Dr. Huh also said that HPV screening resulted in fewer “misses” concerning detection of adenocarcinomas.
Dr. Sawaya said that major guideline groups continue to discourage HPV testing in women younger than 30, and those groups also haven’t weighed in about the value of the cobas HPV strategy of following up a positive test with HPV 16/18 type-specific testing followed by colposcopy, cytology or future follow-up.
The cobas HPV strategy, Dr. Sawaya said, would lead to more positive tests, more surveillance and more confusion and uncertainty, especially for the youngest and oldest who are tested. Screening must maximize benefits while minimizing life disruptions and unnecessary surveillance, treatment and interventions.
Dr. Sawaya talked about the ATHENA study. This U.S.-based, multi-centered study had a main comparison of cobas HPV vs. cytology (ASC-US+). In a cohort of 1,000 women 25 and older with one round of screening, the HPV screening group found CIN 2+ in eight women, while cytology found CIN 2+ in six.
He also questioned cobas HPV sensitivity, which was 45 percent for CIN 2+ in ATHENA. A systematic review of sensitivities for cytology showed a sensitivity between 56 and 71 percent.
The cytology group after a round of screening for the 1,000 women had 10 percent abnormal cytology, 7 percent colposcopy and 5 percent in surveillance. The group following the cobas HPV algorithm had 21 percent HPV positive, 10 percent colposcopy and 19 percent in surveillance. Extended surveillance has adverse psycho-social effects, Dr. Sawaya said.
He suggests screening with cytology alone every three years, with HPV triage for ASC-US.
“The loveliness of this strategy is that after a single screening round, they go to colposcopy or go back to routine screening,” he said. “There’s not this middle ground of coming back in a year. There’s not this uncertainty.” This talk will be available to replay after it airs live. After a short processing delay, it will remain available through the close of the meeting. Simply go to www.acog.org/colloquia.