Pap tests are one of the most familiar — and successful — cancer screening tests ever invented. Since their introduction in the 1950s, cervical cancer deaths have fallen by more than 60 percent in the United States.

But a growing number of scientists say the Pap may be past its prime.

In its place, they are calling for a simple test, one that’s already routinely used as a second-line test around the world: screening for human papillomavirus (HPV).

When the Pap was invented, no one knew what caused cervical cancer. But in the years since, we’ve come to understand that HPV causes almost all cases of cervical cancer, and vaccinating against the virus can essentially obliterate it.

So, testing for HPV would be an upstream way of testing for cervical cancer risk — allowing for earlier detection, cost savings, and even opening the door for at-home testing.

There are signs it’s catching on. Last year, the Netherlands switched from Pap tests to HPV tests, and Australia is set to follow this year. The journal Preventive Medicine devoted an entire issue to HPV testing in February. Clinical trials of at-home HPV testing are underway across the United States, Europe, and Canada.

But some physicians fear the test isn’t good enough to replace the monolithic Pap smear — or feel that, even if it is, we shouldn’t fix what isn’t broken.

Proponents of HPV self-testing say its biggest appeal is in expanding the reach of cancer screenings, both to impoverished areas abroad and to women closer to home.

A trial underway now looks to test that idea in a woefully underserved region of the United States: Appalachia.

“Cervical cancer really is such a cancer of disparities,’’ said Emma McKim Mitchell, lead investigator for the trial. In Appalachian Virginia, those disparities are glaring. The state overall has some of the lowest rates of cervical cancer in the country — but women living in its Appalachian counties are diagnosed with cervical cancer about 13 percent more often than women elsewhere in the state, according to the Appalachia Community Cancer Network.

The women in the study get information about screening and a take-home kit with a long swab and instructions. They insert the swab like a tampon to collect vaginal and cervical cells, put that into an included test tube, and then mail the sample to the lab. There, technicians, instead of looking for precancerous cells as in a Pap test, look for the DNA of the dozen or so carcinogenic HPVs.

A positive HPV test would, in turn, trigger another HPV test the next year. That’s due to the fact that about 90 percent of HPV infections clear on their own.

Two positive tests would then bring women into the clinic.

Mitchell is hopeful that HPV testing could overcome some key barriers that keep Virginian women from being screened: transportation to a clinic and the cost of exams and treatment.

The guidance for US women currently is a patchwork, but it generally coalesces around a few key ideas: Pap smears should start at around age 21, and they should be done every three years if results are normal. If a Pap is paired with an HPV test, then women can go five years between testing. Such co-testing is what most physicians groups recommend for women over 30.

Only one set of guidelines — from the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology — gives the green light to use HPV testing as a primary screening tool, spurred by the introduction of an FDA-approved primary screening test in 2014.

But guidelines are ever-evolving. The US Preventive Services Task Force — one of several organizations that sets cervical cancer screening guidelines — is now reviewing its screening policy and focusing squarely on HPV testing.

In addition to Spain and the Netherlands, where guidelines already recommend HPV testing as the primary test, other countries — including Norway and Australia — are taking steps toward the same goal.

For one thing, some evidence shows that HPV tests are more sensitive than conventional Pap tests, meaning they correctly identify more people at risk for cervical cancer. They may also allow for a longer time between screenings, since they detect the virus before it has the chance to cause cellular changes. That could mean cost savings for health care providers and women themselves.

And using a more sensitive test may become important as the first major cohort to receive the HPV vaccine are now approaching screening age. (The FDA first approved an HPV vaccine for women and girls between 9 and 26 years old in 2006.)

However, the accuracy of HPV testing alone is disputed.

One 2015 study of over 250,000 women, funded by Quest Diagnostics, which offers both forms of cervical cancer screening, found that a whopping 19 percent of cervical cancers were missed by an HPV-only screen. A Pap test missed 12 percent; co-testing missed 5.5 percent. The authors concluded that co-testing was the best approach.

However, Dr. Mark Schiffman, a senior investigator at the National Cancer Institute, takes issue with the study’s methodology. Measuring cancer cases isn’t as good an endpoint as counting cases of both precancerous lesions and cancers, he said.

And timing was problematic, Schiffman said. Specifically, the follow-up time of one year was too short, given the protocols for HPV testing. Typically, women with a positive HPV test wait a year before returning for another test to see if the infection will clear itself.

But the study authors defend their approach. “The key endpoint of screening that determines its effectiveness is cancer,’’ said Dr. Marshall Austin, the medical director of cytopathology at the University of Pittsburgh Medical Center and an author of the study.

One of the models for how wide-scale HPV testing might look is the Netherlands, which began using HPV tests as the primary screening system last year.

If a patient misses an in-clinic HPV test, she receives several follow-up letters. If those letters don’t bring her into the clinic, then one of her next pieces of mail will be a box with a self-sampling kit.

Schiffman worries that such an approach wouldn’t work in the United States. “The main issue, to me, with self-sampling is not a technical one, because technically it’s fine. It’s the organizational structure of how we handle the results that are given out’’ in lieu of a Dutch-style national screening and follow-up program, Schiffman said.

Mitchell has another concern. If at-home testing like the kind being done in her study becomes widespread, might women feel more comfortable skipping regular gynecological exams?

“Providers pack in so much information about so many different systems into those types of visits,’’ she said. “There are opportunities for smoking cessation, intimate partner violence screening — I mean, you name it.’’

Kate Sheridan can be reached at kate.sheridan @statnews.com. Follow her on Twitter @sheridan_kate.