Thursday, May 19, 2016

Is HPV testing ready to replace Pap testing as the first-line test for cervical cancer screening--News from ACOG Annual Clinical and Scientific Meeting 2016.

On Day 3 of the  Annual Clinical and Scientific meeting, ACOG  2016 the question at this year’s John and Marney Mathers Lecture was Is HPV testing ready to replace Pap testing as the first-line test for cervical cancer screening for women 25 and older?

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 are positive about it while 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 morning session debate on May 16, 2016.

Dr. Huh believes that HPV testing has the most sensitivity and negative predictive value out of all the screening technologies. A negative result gives a long time assurance about absence of cervical malignancy. In support of his argument he cited the Canadian cervical cancer screening trial (CCCaST) of 10,171 women ages 30-69 randomized to HPV testing or pap test.  The results showed that verification-bias adjusted sensitivity of Pap cytology was 55.4% while that of HPV testing was 94.7%. Pap test also suffers from variation in collection, storage and lab performance.

He also said “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 its low sensitivity.”

An aggregate of 4 studies published in the Lancet in 2011 found that when all the women who had a normal Pap test were analyzed there was rate of 7.5 instances of cancer per 100,000 women in a year while the same rate for HPV negative patients 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.

Dr. Huh opined that when actually calculated it is 60% risk reduction in cervical cancer over the years. HPV screening further missed less cases when it comes to diagnosis of adenocarcinomas.
The Other Debater Dr. Sawaya said that major groups and association continues to discourage HPV testing in women younger than 30 independent 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.

He is also of the opinion that HPV testing will lead to more surveillance, uncertainty and confusion specially in the younger and the older age groups. A screening test must simplify life by maximizing benefits and avoiding life style disruptions, unnecessary surveillance, treatment and interventions.

He also talked about the ATHENA Trial, a US-based, 3 years’ multicenter study, comparing COBAS HPV vs. cytology (ASC-US+). According to him both techniques are at par when diagnosing CIN 2+ citing that in the ATHENA   trial a cohort of 1000 women, 25+ and older after the first round of screening, the HPV screening group found CIN2+ in eight women, while cytology found CIN 2+ in six.

The cytology group after the screening has had 10 percent abnormal cytology, 7 percent colposcopy and 5 percent in surveillance while those following COBAS algorithm had 21 percent HPV positive, 10 percent colposcopy and 19 percent in surveillance. The increased percentage of patients in surveillance does have increased psychological issues.

He suggests screening with cytology alone every three years, with HPV triage for ASC-US.
He further added “The loveliness of this strategy is that after a single screening round, they go to colposcopy or go back to routine screening. There’s not this middle ground of coming back in a year. There’s not this uncertainty.” 

But, ACOG does updated its guidelines on December 22, 2015 and the practice bulletin is cited here “The Practice Bulletin provides interim guidance on the use of the FDA-approved HPV test for primary cervical cancer screening, which it states can be considered as an alternative to current cytology-based cancer screening methods (the Pap test) in women 25 years and older. Women younger than 25 years should continue to be screened with cytology alone. Additional guidance is included that addresses a number of important clinical issues not specified in the FDA product labeling for the test, including when to rescreen after a negative test result, how to manage positive test results, and when to stop screening in women with negative screening histories.”

In addition, The Society of Gynecologic Oncology (SGO), the American Society for Colposcopy and Cervical Pathology (ASCCP), with input from representatives of five other US national medical organizations (ACOG, ACS, ASCP, ASC, CAP) issued an Interim Guidance Report after the U.S. Food and Drug Administration (FDA) approved the cobas® HPV Test as a primary, or first, test performed for cervical cancer screening.  This new guidance is in addition to the existing 2012 guidelines and specifically addresses the implementation of HPV testing in primary screening.

The guidance recommends:
  • Primary HPV testing can be considered for women starting at age 25.
  • Women with a negative primary HPV test result should not be retested again for at least three years. This is the same screening interval recommended under current guidelines for a normal cytology test result.
  • An HPV test positive for HPV 16 or 18, two types associated with a higher risk of future disease, should be followed with colposcopy.
  • A test that is positive for HPV types other than 16 or 18 should be followed with cytology testing.




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