For now, first still last in primary HPV testing

Karen Titus

October 2015—Not long after the FDA approved a primary HPV screening algorithm for women age 25 and older, in April 2014, things began to stir on the Western front—specifically, in Bellingham, Wash., where Northwest Pathology is based.

“We started offering it pretty much right after the FDA approved it,” says Ryan Fortna, MD, PhD, director of molecular pathology at the regional, independent anatomic pathology group. Though he hasn’t tracked the numbers closely, he estimates primary HPV testing now accounts for maybe five percent of the lab’s overall women’s health testing. The algorithm is based on use of the Roche Cobas HPV assay, and Dr. Fortna says Roche has told him his group was the first in the United States to start offering it. “Which surprised me.”

But all is quiet on the Eastern front—specifically, at Massachusetts General Hospital, reports director of cytopathology Martha Pitman, MD. (She is also associate professor of pathology, Harvard Medical School.) “In our conversations with our GYN clinicians, they have said they’re more interested in cotesting.” She adds, “We really haven’t had a whole lot of conversations about it. They haven’t come to me asking for it. We have never had a request for it.”

There’s still time to beat the rush, in other words.

Mark Stoler, MD, says that based on what he’s hearing from laboratory and clinical colleagues, the algorithm has “slow but steady adoption.” Dr. Stoler, professor emeritus of pathology and clinical gynecology, University of Virginia Health System, Charlottesville, says he knows of a few local clinicians who have started using it, and he’s heard of other large institutions that are close to starting or are at least discussing whether to offer it.

“Slow” is a relative term, of course. In medicine, taking a decade to bring about a change in practice can also be called “normal.” (One pathologist jokes that making changes at her institution is “like moving the Titanic.”)

Says Diane Davey, MD, of the University of Central Florida, Orlando, “It takes awhile for any new testing to percolate down, unless it’s the only test out there.” (Clearly not the case with cervical cancer testing.) “So unless you have a clinician or pathologist who’s promoting it, or clinicians are promoting it in their own practice, it may take a long time,” says Dr. Davey, interim chair, clinical sciences; assistant dean, graduate medical education; and professor of pathology, UCF College of Medicine. She’s also a member of the CAP Cytopathology Committee.

Adds Dr. Stoler: “I think the slowness is a natural byproduct of the fact that we spent 10 years educating people about the advantages of, and the need for, cotesting.”

Breaking from the past

HPV may have the FDA’s blessing as a standalone screen, but it’s not a standalone topic. It’s nearly impossible to talk about primary HPV testing without delving into cotesting, which carries its own baggage. Little wonder, then, that the topic continues to raise its fair share of questions, in addition to reviving old doubts.

In one sense there’s nothing new about the HPV test. “We offered the test anyway, as part of cotesting,” says Dr. Fortna. But it wasn’t business as usual in the primary setting. That’s why Dr. Fortna took careful steps when he began offering the test and asked clinicians to read the fine print (as written by the lab).

The lab retained the HPV testing options already available, but has separated them, spatially, from the new primary testing option, “to make it very clear we’re talking about two different things,” Dr. Fortna says.

“We were very careful with how we worded it on the requisition form,” Dr. Fortna says. This included explaining, in a footnote, what the FDA approval entails. Clinicians can order HPV testing in other scenarios as well, he notes, but the lab wanted to make sure its clients knew exactly what the FDA was stamping with its imprimatur.

Results reporting also underwent a makeover. In cotesting, the cytology result is listed first, with the HPV result below. The recommended action is directly below that. “It follows the logic of, ‘how did you come to this recommendation?’” Dr. Fortna says.

They wanted a different look for reporting primary HPV results, since the logic is different. So “HPV comes first. And in many cases you’re not even reporting a Pap cytology result,” he says. “If you are, it was a reflex from the HPV result.” Consequently, they had to create a new pathway, so to speak, in their laboratory information system. “I don’t know that it’s critical, but we like our reports to make logical sense.”

In this case, finicky follows function. Cervical cancer screening remains a complicated subject, says Dr. Fortna, and he’s found that his clinical colleagues still need help sorting through all the testing options.

“I field questions all the time from clinicians who have trouble understanding the ASCCP algorithms,” says Dr. Fortna. “There’s a whole spectrum with how clinicians deal with this subject.” Some want to follow the algorithms to a T, he says. Others—certain OB-GYNs, for example—use some parts of the algorithms but not others. Family practice physicians, who typically don’t perform as many Pap tests, might want to follow the algorithms but aren’t quite sure how to do it. “And now we’re adding a different algorithm.”

Dr. Fortna isn’t the only one who’s watched physicians go off-roading. Consider:

• “We’re still seeing people do annual Paps, which to me makes no sense when you’ve got cotesting,” says David Wilbur, MD, pathologist, MGH, and professor of pathology, Harvard Medical School.
• “We’re still receiving a significant proportion of patients who are getting cotesting every year, which is overkill if you go by strict recommendations,” says Mohiedean Ghofrani, MD, director of cytopathology, PeaceHealth Laboratories, Vancouver, Wash., and a CAP Cytopathology Committee member.
• Dr. Davey notes that low-risk HPV is not indicated for any kind of cervical cancer screening, yet some physicians may be doing it annually. “That’s not part of any guideline,” she says.
• And from Barbara Crothers, DO, program director of the pathology residency, Walter Reed National Military Medical Center, Bethesda, Md., and chair of the CAP Cytopathology Committee: “We continue to see women who have had a hysterectomy and no history of dysplasia or carcinoma get cotested.”

Nonetheless, the trudge toward modern cervical cancer screening continues. Dr. Stoler says that in debates he’s had with colleagues who are more committed to cytology than to HPV testing, “Nobody is talking about cytology alone. It’s cotesting versus primary HPV as the choice. So that means everybody is getting HPV testing,” he says. “That’s real progress.”

Dr. Ghofrani agrees. The emerging discussions will be whether cotesting will remain the preferred method, or whether primary HPV testing should replace it, he says.

If only it were as simple as deciding which approach is best. It’s not. Physicians need to understand the tradeoffs that accompany each choice, says Dr. Crothers, who led a CAP ’15 panel on HPV testing this month, including an exploration of that topic. “That doesn’t mean that molecular testing primary HPV screening isn’t the way to go,” she says. Rather, physicians need to understand the many issues involved, she says, “so we keep them on the radar screen and make changes down the road as necessary. It’s easy to get lackadaisical and say, ‘OK, issue solved—now we have primary HPV screening.’ It’s actually more complicated than that.”

Getting the word out

Before physicians can choose, they need to know choice exists. After changing the requisition forms, Dr. Fortna and his colleagues at Northwest Pathology sent a letter to all their clinicians who perform Paps, telling them that primary HPV testing was now available. The client services team was also educated so they could talk about it during their visits with physicians. Nonetheless, “Getting the word out is pretty difficult,” says Dr. Fortna, “unless they happen to be particularly interested themselves.” He’s found that some seem interested, and others aren’t. “To be honest, I don’t particularly care if they choose this or cotesting, but we wanted to make it available.”

Dr. Fortna says he regularly fields two questions from clinicians asking about primary HPV testing:

• Why do I want to do this, instead of what I’ve been doing?
• How do I follow up on results?

To the first question, Dr. Fortna’s reply is blunt: “There’s no really good reason, to be honest,” although he immediately adds it has potential to save women money. And, he says, to the extent that people follow the recommendation by starting at age 25, not 30, studies have shown it should help identify a subset of patients with high-grade CIN lesions who would otherwise be missed.

As for the second question, Dr. Fortna says answers have become clearer now that the ASCCP (with the Society of Gynecologic Oncology) has issued its interim guidance on primary HPV testing. (It hadn’t when the laboratory first offered the test.) It basically endorses the short algorithm in the FDA’s publication, says Dr. Fortna.

The report, as listed on the ASCCP website (www.asccp.org), recommends:

• Primary HPV testing can be considered for women starting at age 25.
• Women under age 25 should continue to follow current guidelines that recommend cytology alone beginning at age 21.
• Women with a negative primary HPV test result should not be retested again for 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 and 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 and 18 should be followed by reflex cytology testing.

Dr. Pitman of Massachusetts General hasn’t been encountering questions about primary HPV screening, because no one’s even asking for the test. But she suspects many of her colleagues are waiting to see data from Australia, where the National Cervical Screening Program is shifting, starting in May 2017, to have women age 25 to 74 undergo an HPV test every five years. “It will be interesting to see the outcome of their studies, and how it affects disease detection.”

They may be harboring other reservations as well. Some worry about false-negative HPV test results and what might happen in those intervening three years, Dr. Pitman says.
Finally, she says, “I just don’t think the gynecologists want to completely lose touch with their patients.”

The pull of Pap

Dr. Pitman reports that as cotesting has gained acceptance, her lab has seen a decline in the number of Pap tests and an increase in the number of HPV tests, though the numbers are stable right now. But, as she hints at (and as others have observed), the tug of the annual Pap test remains strong.