In the Journals

Evidence supports HPV testing as screen for cervical cancer, experts say

Researchers laid out the argument for why HPV may be better than the Pap test to screen for cervical cancer, and addressed some concerns that may be hindering the HPV test’s more widespread use.

"HPV testing is coming and the role of cytology will be reduced … this collection of evidence summaries, guidelines, and editorials aims to illustrate the variety of ways the changeover will occur globally,” Mark Schiffman, MD, MPH, senior investigator in the clinical genetics branch at the National Cancer Institute, and guest editor of the special issue of Preventive Medicine, wrote in an editorial. “More broadly, this special issue illustrates the importance and limits of epidemiology as the 'basic science of public health.' The conclusion … is that given an established epidemiologic set of scientific facts and validated prevention tools, real-life concerns that vary by region will determine which public health strategies are used."

Other authors also believe that HPV is a better way to screen for cervical cancer.

“It has … become clear that testing for the causal agent, human papilloma virus (HPV) can bring substantial improvements and efficiency to cervical cancer screening,” Sandra D. Isidean, PhD student, department of oncology, McGill University, Montreal and Gayle A. Shinder, PhD, department of oncology, McGill University, wrote in a second editorial.

Joseph E. Tota, PhD, division of cancer epidemiology and genetics, at the National Cancer Institute, and colleagues noted that though there is “sufficient evidence” for HPV test adoption, most countries have not yet implemented this approach.

“The delay is of particular concern as the first cohorts of vaccinated women are reaching screening age,” Tota and colleagues wrote. “Pap cytology will be an inadequate mainstay of cervical cancer screening for these women, a situation that will be further aggravated after introduction of the nonavalent HPV vaccine.”

Tota and colleagues outlined the advantages of HPV testing: its performance is expected to be less adversely affected as a consequence of reduced lesion frequency; it is better at identifying cervical adenocarcinoma precursor lesions; it allows for self-sampling; it can be automated, more reproducible, and is not subjective; it is more cost-effective; negative HPV tests provide longer, greater reassurance; and is more sensitive than the Pap test in identifying high-grade precancerous lesions.

In a separate report, Nicolas Wentzensen, MD, PhD, division of cancer epidemiology and genetics, National Cancer Institute, and Marc Arbyn, MD, unit of cancer epidemiology, Belgian Cancer Centre in Brussels, addressed the concerns aired for not using the HPV test. These include health care advocates requiring that a new method show feasibility and effectiveness, which Wentzensen and Arbyn pointed out has been well-established with HPV testing in trials in much of the world. They addressed other concerns, such as HPV screening efficacy trials not including cervical cancer endpoints, by stating the rare nature of cervical cancer in existing screening programs makes it difficult to power trials adequately for cancer programs. Another point of contention, that extending the time between cervical cancer screening tests could lead to fewer follow-up visits and leave women without the other benefits these follow-up visits achieve, could be eliminated by creating a “well-organized” program that sends reminders to women about their follow-up care, Wentzensen and Arbyn stated.

“There is overwhelming evidence demonstrating that a HPV-based screening program at longer intervals can be more efficient with potentially fewer screening-related harms compared to cytology screening,” they wrote, adding that three factors should be considered when making the switch to HPV tests: what triage test should be used, what should the screening interval be for HPV-negatives and what HPV screening assay should be used.

In a second report by Tota and colleagues, the authors explored various triage methods associated with HPV, particularly morphologic biomarkers and molecular biomarkers. They stated that using HPV primary screening with genotyping and cytology triage was the most cost-effective when compared with cytology screening (with reflex HPV testing for management of atypical squamous cells of undetermined significance), HPV and cytology co-testing, and HPV primary screening (with reflex to cytology).

“Despite these results, there is currently no obvious winning strategy when it comes to selecting the best triage approach compatible with HPV primary screening,” Tota and colleagues wrote. “We expect the decision will be based on local experience … and successful implementation of HPV primary screening, incorporating either cytology, genotyping plus cytology, or another strategy in similar settings.”

Schiffman stated that although there is a growing mindset towards using HPV testing, the best way to use it is still debatable. He also stated any method chosen must withstand vigorous tests that can be applied to as many different groups as possible.

“I believe that among experts, there is an emerging consensus that HPV testing is theoretically the optimal available primary screening test, but that its optimal implementation is far from settled,” he wrote. “Regardless of what prevention strategy is chosen, it should be scientifically and medically defensible… As different strategies are applied worldwide, the hope is that they will be translatable and represent different societal conclusions sharing a jointly understood scientific base.” – by Janel Miller

Disclosure: Please see the studies for the full list of all authors’ relevant disclosures.

References:

Isidean, SD and Shinder, GA. Prev. Med. 2017:doi:/10.106/jypmed.2016.12.038.

Schiffman, M. Prev Med. 2017:doi:10.1016/j.ypmed.2016.12.028.

Tota JE, et al. Prev Med. 2017:doi:10.1016/j.ypmed.2016.11.029.

Tota JE, et al. Prev Med. 2017:doi:10.1016/j.ypmed.2016.11.030.

Wentzsen, N, et al. Prev Med. 2017:doi:10.106/jypmed.2016.12.040.

 

Researchers laid out the argument for why HPV may be better than the Pap test to screen for cervical cancer, and addressed some concerns that may be hindering the HPV test’s more widespread use.

"HPV testing is coming and the role of cytology will be reduced … this collection of evidence summaries, guidelines, and editorials aims to illustrate the variety of ways the changeover will occur globally,” Mark Schiffman, MD, MPH, senior investigator in the clinical genetics branch at the National Cancer Institute, and guest editor of the special issue of Preventive Medicine, wrote in an editorial. “More broadly, this special issue illustrates the importance and limits of epidemiology as the 'basic science of public health.' The conclusion … is that given an established epidemiologic set of scientific facts and validated prevention tools, real-life concerns that vary by region will determine which public health strategies are used."

Other authors also believe that HPV is a better way to screen for cervical cancer.

“It has … become clear that testing for the causal agent, human papilloma virus (HPV) can bring substantial improvements and efficiency to cervical cancer screening,” Sandra D. Isidean, PhD student, department of oncology, McGill University, Montreal and Gayle A. Shinder, PhD, department of oncology, McGill University, wrote in a second editorial.

Joseph E. Tota, PhD, division of cancer epidemiology and genetics, at the National Cancer Institute, and colleagues noted that though there is “sufficient evidence” for HPV test adoption, most countries have not yet implemented this approach.

“The delay is of particular concern as the first cohorts of vaccinated women are reaching screening age,” Tota and colleagues wrote. “Pap cytology will be an inadequate mainstay of cervical cancer screening for these women, a situation that will be further aggravated after introduction of the nonavalent HPV vaccine.”

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Tota and colleagues outlined the advantages of HPV testing: its performance is expected to be less adversely affected as a consequence of reduced lesion frequency; it is better at identifying cervical adenocarcinoma precursor lesions; it allows for self-sampling; it can be automated, more reproducible, and is not subjective; it is more cost-effective; negative HPV tests provide longer, greater reassurance; and is more sensitive than the Pap test in identifying high-grade precancerous lesions.

In a separate report, Nicolas Wentzensen, MD, PhD, division of cancer epidemiology and genetics, National Cancer Institute, and Marc Arbyn, MD, unit of cancer epidemiology, Belgian Cancer Centre in Brussels, addressed the concerns aired for not using the HPV test. These include health care advocates requiring that a new method show feasibility and effectiveness, which Wentzensen and Arbyn pointed out has been well-established with HPV testing in trials in much of the world. They addressed other concerns, such as HPV screening efficacy trials not including cervical cancer endpoints, by stating the rare nature of cervical cancer in existing screening programs makes it difficult to power trials adequately for cancer programs. Another point of contention, that extending the time between cervical cancer screening tests could lead to fewer follow-up visits and leave women without the other benefits these follow-up visits achieve, could be eliminated by creating a “well-organized” program that sends reminders to women about their follow-up care, Wentzensen and Arbyn stated.

“There is overwhelming evidence demonstrating that a HPV-based screening program at longer intervals can be more efficient with potentially fewer screening-related harms compared to cytology screening,” they wrote, adding that three factors should be considered when making the switch to HPV tests: what triage test should be used, what should the screening interval be for HPV-negatives and what HPV screening assay should be used.

In a second report by Tota and colleagues, the authors explored various triage methods associated with HPV, particularly morphologic biomarkers and molecular biomarkers. They stated that using HPV primary screening with genotyping and cytology triage was the most cost-effective when compared with cytology screening (with reflex HPV testing for management of atypical squamous cells of undetermined significance), HPV and cytology co-testing, and HPV primary screening (with reflex to cytology).

“Despite these results, there is currently no obvious winning strategy when it comes to selecting the best triage approach compatible with HPV primary screening,” Tota and colleagues wrote. “We expect the decision will be based on local experience … and successful implementation of HPV primary screening, incorporating either cytology, genotyping plus cytology, or another strategy in similar settings.”

Schiffman stated that although there is a growing mindset towards using HPV testing, the best way to use it is still debatable. He also stated any method chosen must withstand vigorous tests that can be applied to as many different groups as possible.

“I believe that among experts, there is an emerging consensus that HPV testing is theoretically the optimal available primary screening test, but that its optimal implementation is far from settled,” he wrote. “Regardless of what prevention strategy is chosen, it should be scientifically and medically defensible… As different strategies are applied worldwide, the hope is that they will be translatable and represent different societal conclusions sharing a jointly understood scientific base.” – by Janel Miller

Disclosure: Please see the studies for the full list of all authors’ relevant disclosures.

References:

Isidean, SD and Shinder, GA. Prev. Med. 2017:doi:/10.106/jypmed.2016.12.038.

Schiffman, M. Prev Med. 2017:doi:10.1016/j.ypmed.2016.12.028.

Tota JE, et al. Prev Med. 2017:doi:10.1016/j.ypmed.2016.11.029.

Tota JE, et al. Prev Med. 2017:doi:10.1016/j.ypmed.2016.11.030.

Wentzsen, N, et al. Prev Med. 2017:doi:10.106/jypmed.2016.12.040.