HPV test better than Pap smear at detecting precancerous changes

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HPVtestA test for HPV detects precancerous changes of the cervix earlier and more accurately than the Pap smear, according to a large clinical trial. The Washington Post reports that the randomised, controlled study 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 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 gynaecologic oncologist at New York-Presbyterian/Columbia University Medical Centre 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.

The HPV infection is the most common sexually transmitted infection and is usually eliminated by the immune system within a year or two. 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.

The report says the study bolsters previous research that showed that HPV testing was superior to Pap tests. Over the past several years, as experts learned more about HPV’s role in cervical cancer, most medical groups have recommended that women in the US get both the HPV test and the Pap smear — a practice called “co-testing.” Now, armed with the new study and previous ones, 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 – such as 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 gynaecological oncologist at MD Anderson Cancer Centre 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, the report says, Mark Spitzer, a gynaecologist in New Hyde Park, New York, and past president of the American Society for Colposcopy and Cervical Pathology, disagreed. He said that although the study confirmed previous research, 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 report says in the US, the conventional Pap smear has been largely replaced by a liquid-based Pap cytology test. Cervical cells for both the Pap and HPV tests can be collected at the same time, during a pelvic exam. Some women might not even realise that they are being tested for HPV.

The decade-long study 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 Pap 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 with the Pap cytology group.

The report says the study 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 test. The researchers reported that there were fewer cases of precancer in the HPV test group, compared with 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 study, funded by the Canadian Institute of Health Research, noted that adding HPV testing 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 support 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 the HPV test 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 causing the problem. The Pap smear worked, he said, only because women were tested often and because cervical cancer grows slowly.

The report says most medical groups, including the American Cancer Society and the American College of Obstetricians and Gynaecologists, 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 80m people in the US are infected with HPV, but most never develop any health problems because most infections go away by themselves, according to the Centres 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, as well as cancer of the penis.

The report says that’s why doctors strongly recommend that children and young adults be vaccinated against HPV; a vaccine was approved by the US 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 US, according to a study that also found that there was a decrease in HPV infections among women 20 to 24.

Importance: There is limited information about the relative effectiveness of cervical cancer screening with primary human papillomavirus (HPV) testing alone compared with cytology in North American populations.
Objective: To evaluate histologically confirmed cumulative incident cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) detected up to and including 48 months by primary HPV testing alone (intervention) or liquid-based cytology (control).
Design, Setting, and Participants: Randomized clinical trial conducted in an organized Cervical Cancer Screening Program in Canada. Participants were recruited through 224 collaborating clinicians from January 2008 to May 2012, with follow-up through December 2016. Women aged 25 to 65 years with no history of CIN2+ in the past 5 years, no history of invasive cervical cancer, or no history of hysterectomy; who have not received a Papanicolaou test within the past 12 months; and who were not receiving immunosuppressive therapy were eligible.
Interventions: A total of 19 009 women were randomized to the intervention (n = 9552) and control (n = 9457) groups. Women in the intervention group received HPV testing; those whose results were negative returned at 48 months. Women in the control group received liquid-based cytology (LBC) testing; those whose results were negative returned at 24 months for LBC. Women in the control group who were negative at 24 months returned at 48 months. At 48-month exit, both groups received HPV and LBC co-testing.
Main Outcomes and Measures: The primary outcome was the cumulative incidence of CIN3+ 48 months following randomization. The cumulative incidence of CIN2+ was a secondary outcome.
Results: Among 19 009 women who were randomized (mean age, 45 years [10th-90th percentile, 30-59]), 16 374 (8296 [86.9%] in the intervention group and 8078 [85.4%] in the control group) completed the study. At 48 months, significantly fewer CIN3+ and CIN2+ were detected in the intervention vs control group. The CIN3+ incidence rate was 2.3/1000 (95% CI, 1.5-3.5) in the intervention group and 5.5/1000 (95% CI, 4.2-7.2) in the control group. The CIN3+ risk ratio was 0.42 (95% CI, 0.25-0.69). The CIN2+ incidence rate at 48 months was 5.0/1000 (95% CI, 3.8-6.7) in the intervention group and 10.6/1000 (95% CI, 8.7-12.9) in the control group. The CIN2+ risk ratio was 0.47 (95% CI, 0.34-0.67). Baseline HPV-negative women had a significantly lower cumulative incidence of CIN3+ at 48 months than cytology-negative women (CIN3+ incidence rate, 1.4/1000 [95% CI, 0.8-2.4]; CIN3+ risk ratio, 0.25 [95% CI, 0.13-0.48]).
Conclusions and Relevance: Among women undergoing cervical cancer screening, the use of primary HPV testing compared with cytology testing resulted in a significantly lower likelihood of CIN3+ at 48 months. Further research is needed to understand long-term clinical outcomes as well as cost-effectiveness.

Gina Suzanne Ogilvie; Dirk van Niekerk; Mel Krajden; Laurie W Smith; Darrel Cook; Lovedeep Gondara; Kathy Ceballos; David Quinlan; Marette Lee; Ruth Elwood Martin; Laura Gentile; Stuart Peacock; Gavin CE Stuart; Eduardo L Franco; Andrew J Coldman

The Washington Post report
JAMA abstract

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