A two-part Bulletin series

Today: Annual pap smears come with risk of harm for those at low risk for cervical cancer.

Monday: Are physicians ignoring guidelines for medical reasons or financial ones?

For years doctors have urged women to come in for annual pap smear testing to screen for cervical cancer. But over the past decade, women’s health experts have recognized that such frequent testing not only doesn’t provide greater protection from cancer, it may be causing serious medical harm.

Guidelines from groups including the American Cancer Society, the U.S. Preventive Health Services Task Force and the American College of Obstetricians and Gynecologists recommend less frequent testing for women at low risk for cervical cancer. Yet physician surveys and analyses of medical and billing records show that a significant percentage of doctors are still bringing women back year after year for a pap test.

“We understand the natural history of cervical cancer much better than any other cancer,” said Dr. Mark Einstein, director of clinical research for women’s health and gynecologic oncology at the Albert Einstein Cancer Center in the Bronx, New York. “And what we’ve learned is the way we used to do pap testing, while it was highly effective, we were also causing a lot of potential harm to patients.”

The pap test has been in place for more than 50 years and has been remarkably successful in driving down rates of cervical cancer. Before pap testing, cervical cancer was the No. 1 cancer killer of women, Einstein said, and now it doesn’t rank in the top 10.

“We’ve gotten to the point where we’ve realized we can’t do much better (at preventing cancer) with our current screening,” he said. “But maybe we could do better by just eliminating harm, and so we started spacing out how we do this.”

Harm arises when a woman has a false positive pap test result and is referred for colposcopy, a more extensive test to look for cancer or precancerous lesions. Guideline-setting groups use the number of colposcopies as a measure of harm, because the procedure is a necessary prerequisite for more invasive treatments. They start women down the road toward biopsies and treatments that carry a risk of bleeding and infection in the short term, and an increased risk of pregnancy complications, such as preterm delivery or infertility, later on.

Although the risk of harm is small, and certainly outweighed for women who actually have cancer, the high rate of false positives in pap tests means many women undergoing colposcopy are subjected to unneeded treatments and their resulting risks. One review found that women who undergo treatment for cervical lesions have a 70 percent to 160 percent increased risk for preterm delivery, as well as higher risk for low birth weight, premature rupture of membranes and C-sections.

In the 2012 guidelines, the groups calculated that screening women every three years instead of every year would result in two to five additional cancer diagnoses for every 1,000 women, although with the high survival rate, only two additional deaths per 100,000 women. On the other hand, annual screening would result in nearly three times as many colposcopies.

Because cervical cancer is relatively slow to develop, screening every year is unlikely to catch many more lesions or cancers than screening every three to five years. Meanwhile, the discovery that cervical cancer is caused by the human papillomavirus, or HPV, has led to more accurate screening tests that detect the virus directly. That in turn allows doctors to better stratify women as high- or low-risk for cervical cancer, and tailor their screening regimen going forward.

Professional societies now back simultaneous pap and HPV tests every five years from age 30 to 65, unless patients test positive at some point or fall into certain high-risk groups. A less-effective alternative, although still acceptable under the guidelines, is pap tests alone every three years. The guidelines call for screening women 21 to 30 with pap testing every three years, because they are likely to have HPV infections that will clear on their own.

Poor compliance

Physicians have been slow to adopt the new guidelines. In 2012, researchers from the Feinberg School of Medicine at Northwestern University mined electronic health records at one Midwestern clinic to see how well doctors were following the screening guidelines. They found that out of 1,705 women who met the criteria for extended screening, 66 percent had a second pap test done within the following two years, and 25 percent had tests done both years.

Those additional 1,551 pap tests resulted in 21 women undergoing colposcopy, with 20 women getting negative results. The additional tests identified one woman with adenocarcinoma in situ, a precancerous condition that is generally treated with hysterectomy. It is possible the woman could have had the same outcome had she waited. It can take months or years for invasive cancer to develop from this initial stage. But the researchers acknowledged the woman might have been harmed if she had not been screened for another year.

“This is a predictable consequence of less frequent screening,” the researchers wrote.

Trade-offs like these make the balance of benefits and harm in screening a tricky business. Doctors could do such frequent screening that virtually no cancer would escape detection, but that could come at a heavy financial cost and with many unintended patient harms. Instead the guidelines try to find the screening interval that will offer the best mix of maximizing cancer protection while minimizing harm.

That balance could be upset when physicians opt for shorter screening intervals. Yet a 2011 survey of physicians by researchers at the Centers for Disease Control and Prevention found either widespread ignorance or woeful disregard of the screening guidelines. Less than a third of doctors reported that they would lengthen screening intervals to three years in a 35-year-old woman with three normal pap test results and no new sexual partners, as the 2003 guidelines recommended. Fewer than one in five would lengthen screening intervals to three years in the same patient with a normal pap test and a negative HPV test as recommended starting in 2004.

Doctors may be reluctant to move to less frequent testing because of the financial incentives. (Read more about this Monday.) Or they may believe they are providing women better protection with annual screening.

“Old habits die hard,” said Dr. Natalie Hoshow, a gynecologist with St. Charles Health System in Bend. “That’s true for physicians as well.”

Hoshow said she customizes screening intervals according to a woman’s age and risk. In women over 30 with negative pap and HPV tests, she will screen again in three years. For women age 21 to 30, with a high risk of HPV infection, she will conduct pap tests every year or two.

There are some signs that more doctors and patients might be coming around. In Oregon, cervical screening rates for women 18 to 39 dropped from 33 percent in 2009 to 25 percent in 2012.

“Most of that decline,” said Dr. Sean Schafer, an epidemiologist with the Oregon Department of Human Services, “happened in women 18 to 20,” who are too young to be screened under the guidelines.

Three protocols

The variability in screening may intensify now that the FDA has approved the first HPV test that can be used alone for primary cervical cancer screening, potentially eliminating pap tests altogether for those patients. Studies have shown that HPV screening alone is almost as good as doing both tests, and that adding a pap test may not be worth the added costs.

Professional societies plan to issue interim guidance for the HPV test this summer. They must still sort out the best age to start screening with HPV tests, and how to manage women who test positive for an HPV strain, but then have a normal follow-up pap test. And they must determine which screening interval will provide the greatest benefits with the least amount of harm.

Individuals familiar with the societies’ discussions say the guidance is likely to add screening through HPV alone as a third option alongside pap tests alone or doing both tests, rather than to recommend all providers move to primary screening with the HPV test.

Data from Kaiser Permanente Northern California’s use of HPV testing showed that HPV testing every three years provided better protection than the current recommendations for pap tests every three years or doing both tests every five years.

“There is really a greater reassurance in a negative HPV test than a negative pap,” said Dr. Julia Gage, a National Cancer Institute epidemiologist who analyzed data from Kaiser’s use of HPV tests in northern California. “Many settings are still using primary pap testing, and this could be a definite viable alternative.”

Australia and many European countries have already announced plans to move to HPV screening alone with screening intervals anywhere from three to seven years. Many suspect the U.S. will eventually move in that direction. The interim guidance is also likely to leave the U.S. as the only country with three different screening protocols. It also means women may move between screening protocols when they change doctors.

“We have concerns that introducing a third screening paradigm will cause a huge amount of confusion,” said Dr. David Chelmow, a professor of obstetrics and gynecology at Virginia Commonwealth University, who spoke at an FDA advisory committee meeting earlier this year on behalf of the American College of Obstetricians and Gynecologists. “We already know that people have not caught on to the new paradigms that went into place two years ago, and actually some of them didn’t catch on to the ones that were in place before that.”

Patient reluctance

Patients who have become accustomed to yearly tests, however, can see a longer screening interval as less protection.

“When we interview women, they think that the provider who is telling them to extend the screening interval is doing it to save money and it’s not really in their best benefit,” said Dr. Mona Saraiya, a CDC epidemiologist. “(They believe) it’s more about the government cutting back.”

Providers who take the time to explain why an extended screening time is safer, however, have found women are generally receptive. Kaiser found that 92 percent of women were fine with the longer intervals.

“When these extended intervals came out, we heard from women in droves who were like, ‘Oh my gosh, what do you mean I don’t need to get my annual pap smear?’” said Fred Wyand, director of communications for the National Cervical Cancer Coalition. “There’s a big piece with both providers and patients to make sure they understand not only what the new guidelines are, but the rationale behind it.”

It represents a major pivot for women’s health advocates.

“We finally feel we’ve got the message across and now we’re changing the recommendation,” said Dr. Wendy Brewster, an associate professor at the University of North Carolina School of Medicine and spokeswoman for the Society of Gynecological Oncology.

As confusing as the changes are for both doctors and patients, the bottom line, she said, is that HPV testing will allow doctors to find more lesions before they progress to cancer and help women avoid unnecessary tests by better stratifying their risk of cervical cancer.

Broader acceptance of HPV testing and its longer screening intervals may require a concerted education effort for doctors and their patients, so that women aren’t left to feel they are less safe with less screening.

“It’s the difference between your care being rationed and your care being tailored based on new information,” Brewster said. “We can hone in because this wonderful test has identified you as somebody who is at increased risk. We’re tailoring your care. It’s personalized medicine. It’s what everybody wants.”

Women’s health advocates also emphasize that any sort of testing is better than no testing at all. Of the more than 12,000 women who are diagnosed with cervical cancer in the U.S. each year, 54 percent have never been screened, and 12 percent had a positive test result but never followed up for further testing. Less than a third of cancers were missed by screening.

In the long run, the landscape may change significantly as more women are vaccinated against HPV, and newer iterations of the vaccine protect against more strains of HPV. Doctors started vaccinating teens in 2006, but only a small percentage of girls have been vaccinated. In 2013, only 57 percent of girls 13 to 17 had received at least one dose of the vaccine. Cervical cancer screening in the U.S. takes place in a largely unvaccinated population, a dynamic public health officials hope will change in the coming decades.

The push on vaccination has also helped pave the way for HPV testing to replace pap tests by driving home the message that it’s the virus that causes cervical cancer. Now if a similar campaign helps women understand the risks associated with yearly screening, it could further improve women’s health.

“I really do hope the annual pap goes away,” Brewster said. “I do think we have other tools that are better.”

— Reporter: 541-617-7814, mhawryluk@bendbulletin.com