A test for HPV detects precancerous changes of the cervix earlier and more accurately than the Pap smear, according to a large clinical trial published Tuesday.

The randomized, controlled study — the kind of trial considered the “gold standard” of research — showed that the human papillomavirus test is more sensitive than the Pap smear, a widely used test that has been a standard part of women’s preventive health care for decades but has several drawbacks.

Several experts predicted the results would spur efforts to entirely replace the Pap test with the HPV test. “It’s an important study,” said Jason Wright, a gynecologic oncologist at NewYork-Presbyterian/Columbia University Medical Center who was not involved in the study. “It shows that doing HPV testing alone provides a high degree of accuracy” on who might be at risk for cervical cancer.

HPV is the most common sexually transmitted infection, and is usually eliminated by the immune system within a year or two year. But when an infection persists, it can cause cellular changes that develop into precancerous lesions and, eventually, malignancies. Almost all cases of cervical cancer are caused by HPV infections.

About 13,240 new cases of invasive cervical cancer will be diagnosed in the United States in 2018, according to the American Cancer Society. About 4,200 women will die of the disease.

Over the last several years, as experts learned more about HPV’s role in cervical cancer, most medical groups have recommended that women in the United States get both the HPV test and the Pap smear — a practice called “co-testing.” Now, armed with the new and previous studies, some experts say the Pap smear should be dropped. But others disagree, saying that the Pap smear can catch a small number of cases of abnormal cells that might be missed by the HPV test and that co-testing should continue.

Many of the medical groups have said that before moving to HPV-testing only, they needed to see clinical trial results — like the kind provided by the new head-to-head study — to determine which test, over time, was better at detecting the precancerous changes. These conditions can be treated before they progress to cervical cancer.

Kathleen Schmeler, a gynecological oncologist at MD Anderson Cancer Center who was not involved in the study was enthused about the new results. “It’s fantastic,” she said. “What this shows is that you could potentially do just the HPV test and move toward getting rid of the Pap test.”

But Mark Spitzer, a gynecologist in New Hyde Park, New York, and past president of the American Society for Colposcopy and Cervical Pathology, disagreed. He said that while the study confirmed previous studies showing that the HPV test is more sensitive than the Pap test, it didn’t answer a critical question: Is the HPV test alone better than the HPV test and the Pap smear together, as is current practice?

The decade-long study, which appeared in JAMA, involved about 19,000 women who were placed in two groups: One using the HPV test to screen for cervical cancer and the other using a kind of Pap test called liquid-based cytology. In 2017, the researchers running the study reported that there were significantly more cases of precancerous lesions detected early in the trial among the women in the HPV-tested group compared to the Pap cytology group.

Tuesday’s report detailed the “exit” results of the study 48 months after the women were enrolled and first screened. For those final results, both groups were tested using both the HPV test and the Pap smear.

The researchers reported that there were fewer cases of pre-cancer in the HPV test group compared to the Pap smear group. That’s because cases of worrisome cellular changes already had been detected and dealt with after the women were first screened, said lead author Gina Ogilvie, a physician and public health researcher at the University of British Columbia. “The real benefit of co-testing is with the HPV test,” she said.

The paper noted that adding HPV test to the Pap test group resulted in finding 25 lesions that would have not been found by the Pap test alone. By adding the Pap test to the HPV group, an additional three lesions were found.

Spitzer said those three cases “supports the small but significant benefit of co-testing.”

The National Cancer Institute’s Mark Schiffman, who has done extensive research on HPV, said the study confirmed that it’s important to move from the Pap smear to HPV alone. “This has been building for decades,” he said, adding that the Pap smear is “crude and inaccurate” while the HPV test is much more precise, operates on the molecular level, and can provide information on the specific type of HPV that is causing the problem. The Pap smear only worked, he said, because women were tested often and cervical cancer grows slowly.

Most medical groups including the American Cancer Society and the American College of Obstetricians and Gynecologists recommend that women of average risk get both HPV tests and Pap smears every five years between age 30 and 65, though they say a Pap test alone every three years is an acceptable alternative. Women in their 20s are advised to get Pap smears, not HPV tests, because the virus is so common that most would test positive for infections that would most likely clear up on their own.

About 80 million people in the United States are infected with HPV, but most never develop any health problems because most infections go away by themselves, according to the Centers for Disease Control and Prevention. But when infections last longer, they can cause not only cervical cancer but also cancer of the anus, and back of the throat and well as cancer of the penis in men.

That’s why doctors strongly recommend that children and young adults be vaccinated against HPV; a vaccine was approved by the Food and Drug Administration in 2006. Infection with HPV types targeted by the vaccine has declined by nearly two-thirds among teenage girls since HPV vaccination was recommended in the United States, according to a study which also found that there was a decrease in HPV infections among women 20 to 24.

The United States Preventive Services Task Force, an independent panel that reviews the evidence of effectiveness for preventive services, currently recommends the “co-testing” that other groups advocate. But last fall, it issued a draft recommendation proposing that women undergo either HPV testing every five years or Pap smears every three years, but a final recommendation has not been released.

The new study will likely “help push that along,” Wright of NewYork-Presbyterian/Columbia University Medical Center. He called use of the HPV test only a “reasonable strategy,” but noted that the test’s strength — its sensitivity — could result in more positive results and more testing. Partly because of that, he said, “We’re a long way away from replacing the Pap smear.”