In the Journals

HPV testing after abnormal cytology hastens detection of cervical precancer

HPV testing after abnormal cytology resulted in earlier detection of high-grade cervical intraepithelial neoplasia lesions, according to results of an observational study.

“This study shows that knowing a woman’s HPV status can help determine her likelihood of needing additional procedures, and prioritizes immediate treatment and medical resources to the women who need them most,” Jack Cuzick, PhD, director of the Wolfson Institute of Preventive Medicine at Queen Mary University of London, said in a press release.

Jack Cuzick

The American Society for Colposcopy and Cervical Pathology recommends reflex HPV testing for atypical squamous cells of undetermined significance cytology in women aged 25 years and older and repeat cytology for those aged 21 to 24 years. However, long-term benefits and harms of routine HPV testing remain unknown.

Cuzick and colleagues from the New Mexico HPV Pap Registry Steering Committee previously studied the influence of HPV testing on biopsies and repeat cytology in New Mexico, showing that 80% of women aged 30 to 64 years with atypical squamous cells of undetermined significance underwent HPV testing. HPV co-testing occurred in fewer than 20% of women but appeared to be rapidly increasing.

In the current analysis, researchers focused on the histologic 5-year cervical intraepithelial neoplasia (CIN) outcomes after atypical squamous cells of undetermined significance cytology screening between 2008 and 2012 among women aged 21 to 64 years. Study aims included to determine the influence of HPV triage on the 5-year rate of high-grade lesions, how HPV testing affected the interval between abnormal screening cytology and the detection of high-grade CIN, and the extent to which HPV leads to overdetection and overtreatment of low-grade lesions.

The researchers evaluated statewide cervical cytology and HPV testing reports of 457,317 women (mean age, 39.8 years) from nine laboratories in New Mexico and nine out-of-state laboratories between January 2007 and December 2012. They linked pathology reports for biopsy outcomes, obtained through December 2013 to allow a minimum follow-up of 1 year. The analysis occurred from May 4, 2015, to Jan. 13, 2017.

The first cytology results per woman included 20,677 cases (4.5%) of atypical squamous cells of undetermined significance.

Patients who underwent HPV testing showed a higher detection rate of CIN grade 3 or more severe (CIN3+) lesions (2.42% vs. 2.15%); this equated to more than a 15.8% increase in early detection (RR = 1.16; 95% CI, 0.92-1.45).

In the first year of follow-up, women who underwent HPV testing had a shorter time to CIN3+ detection (median, 103 vs. 393 days; P<.001).

Absolute difference in detection decreased from 0.56% (RR = 1.6; 95% CI, 1.14-2.25) in the first year to 0.34% by year 5 (RR = 1.16; 95% CI, 0.92-1.45).

“Therefore, most CIN [grade 3 or more severe] lesions were persistent and are eventually detected even without HPV triage,” the researchers wrote.

HPV testing also improved detection of CIN2+ lesions (3% vs. 1.6%; RR = 1.82; 95% CI, 1.41-2.35) and CIN grade 1 lesions (11.6% vs. 6.6%; RR = 1.76; 95% CI, 1.56-2).

Biopsy rates appeared 55% higher and loop electrosurgical excision procedure rates within 5 years appeared 20% higher among women who underwent HPV testing.

“The cost is a higher biopsy rate, which is a minor procedure, but worth avoiding if possible,” Cuzick told HemOnc Today. “New tests are in development to identify more women who do not have significant disease and who do not need immediate colposcopy.”

The present strategy of HPV triage improved detection of high-grade and low-grade lesions in a shorter amount of time. However, it required more biopsies and whether it prevented cervical cancer remained unclear, Chris J. L. M. Meijer, MD, PhD, and Peter J. F. Snijders, PhD, both from the department of pathology at VU University Medical Center in Amsterdam, The Netherlands, wrote in a related editorial.

“The underlying essential question is does this screening strategy prevent more cervical cancer, or (otherwise said) what is the influence of HPV triage on cervical cancer rates?” Meijer and Snijders wrote. “Unfortunately, the article by Cuzick [and colleagues] cannot answer this question, because the number of carcinomas detected in the described population was too small to obtain a reliable answer.”

Although Cuzick and colleagues expected the influence of their study to be small due to the similar 5-year detection rates of significant lesions between the groups, Meijer and Snijders said being able to answer this question is of “utmost importance” to balance earlier detection with overtreatment.

Regardless, the data provide basis for further monitoring of this balance in U.S. cervical screening practice, they wrote.

“The study results may lead to recommendation of less intense screening strategies with similar benefits and less harms,” Meijer and Snijders wrote. – by Melinda Stevens

For more information:

Jack Cuzick, PhD, can be reached at j.cuzick@qmul.ac.uk.

Disclosure: Cuzick reports advisory or speaker fees from Abbott, Becton Dickinson, Cepheid, Merck and Trovagene; and institutional grants from Abbott, Becton Dickinson, Cepheid, Hologic, OncoHealth, Qiagen and Trovagene during the time of the study. Please see the full study for a list of all other researchers’ relevant financial disclosures. Meijer reports speaker fees from GlaxoSmithKline, Menarini, Qiagen, Roche Diagnostics, Sanofi Pasteur-MSD/Merck and Seegene; consultant/advisory roles with Genticel, GlaxoSmithKline, Qiagen, Roche and Sanofi Pasteur-MSD/Merck; and minority shareholder roles with Dissay B.V. and Self-Screen B.V. Snijders reports a minority shareholder role with Self-Screen B.V.; speaker roles with Abbott, Gen-Probe, Qiagen, Roche Diagnostics and Seegene; and a consultant role with Crucell B.V.

HPV testing after abnormal cytology resulted in earlier detection of high-grade cervical intraepithelial neoplasia lesions, according to results of an observational study.

“This study shows that knowing a woman’s HPV status can help determine her likelihood of needing additional procedures, and prioritizes immediate treatment and medical resources to the women who need them most,” Jack Cuzick, PhD, director of the Wolfson Institute of Preventive Medicine at Queen Mary University of London, said in a press release.

Jack Cuzick

The American Society for Colposcopy and Cervical Pathology recommends reflex HPV testing for atypical squamous cells of undetermined significance cytology in women aged 25 years and older and repeat cytology for those aged 21 to 24 years. However, long-term benefits and harms of routine HPV testing remain unknown.

Cuzick and colleagues from the New Mexico HPV Pap Registry Steering Committee previously studied the influence of HPV testing on biopsies and repeat cytology in New Mexico, showing that 80% of women aged 30 to 64 years with atypical squamous cells of undetermined significance underwent HPV testing. HPV co-testing occurred in fewer than 20% of women but appeared to be rapidly increasing.

In the current analysis, researchers focused on the histologic 5-year cervical intraepithelial neoplasia (CIN) outcomes after atypical squamous cells of undetermined significance cytology screening between 2008 and 2012 among women aged 21 to 64 years. Study aims included to determine the influence of HPV triage on the 5-year rate of high-grade lesions, how HPV testing affected the interval between abnormal screening cytology and the detection of high-grade CIN, and the extent to which HPV leads to overdetection and overtreatment of low-grade lesions.

The researchers evaluated statewide cervical cytology and HPV testing reports of 457,317 women (mean age, 39.8 years) from nine laboratories in New Mexico and nine out-of-state laboratories between January 2007 and December 2012. They linked pathology reports for biopsy outcomes, obtained through December 2013 to allow a minimum follow-up of 1 year. The analysis occurred from May 4, 2015, to Jan. 13, 2017.

The first cytology results per woman included 20,677 cases (4.5%) of atypical squamous cells of undetermined significance.

Patients who underwent HPV testing showed a higher detection rate of CIN grade 3 or more severe (CIN3+) lesions (2.42% vs. 2.15%); this equated to more than a 15.8% increase in early detection (RR = 1.16; 95% CI, 0.92-1.45).

In the first year of follow-up, women who underwent HPV testing had a shorter time to CIN3+ detection (median, 103 vs. 393 days; P<.001).

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Absolute difference in detection decreased from 0.56% (RR = 1.6; 95% CI, 1.14-2.25) in the first year to 0.34% by year 5 (RR = 1.16; 95% CI, 0.92-1.45).

“Therefore, most CIN [grade 3 or more severe] lesions were persistent and are eventually detected even without HPV triage,” the researchers wrote.

HPV testing also improved detection of CIN2+ lesions (3% vs. 1.6%; RR = 1.82; 95% CI, 1.41-2.35) and CIN grade 1 lesions (11.6% vs. 6.6%; RR = 1.76; 95% CI, 1.56-2).

Biopsy rates appeared 55% higher and loop electrosurgical excision procedure rates within 5 years appeared 20% higher among women who underwent HPV testing.

“The cost is a higher biopsy rate, which is a minor procedure, but worth avoiding if possible,” Cuzick told HemOnc Today. “New tests are in development to identify more women who do not have significant disease and who do not need immediate colposcopy.”

The present strategy of HPV triage improved detection of high-grade and low-grade lesions in a shorter amount of time. However, it required more biopsies and whether it prevented cervical cancer remained unclear, Chris J. L. M. Meijer, MD, PhD, and Peter J. F. Snijders, PhD, both from the department of pathology at VU University Medical Center in Amsterdam, The Netherlands, wrote in a related editorial.

“The underlying essential question is does this screening strategy prevent more cervical cancer, or (otherwise said) what is the influence of HPV triage on cervical cancer rates?” Meijer and Snijders wrote. “Unfortunately, the article by Cuzick [and colleagues] cannot answer this question, because the number of carcinomas detected in the described population was too small to obtain a reliable answer.”

Although Cuzick and colleagues expected the influence of their study to be small due to the similar 5-year detection rates of significant lesions between the groups, Meijer and Snijders said being able to answer this question is of “utmost importance” to balance earlier detection with overtreatment.

Regardless, the data provide basis for further monitoring of this balance in U.S. cervical screening practice, they wrote.

“The study results may lead to recommendation of less intense screening strategies with similar benefits and less harms,” Meijer and Snijders wrote. – by Melinda Stevens

For more information:

Jack Cuzick, PhD, can be reached at j.cuzick@qmul.ac.uk.

Disclosure: Cuzick reports advisory or speaker fees from Abbott, Becton Dickinson, Cepheid, Merck and Trovagene; and institutional grants from Abbott, Becton Dickinson, Cepheid, Hologic, OncoHealth, Qiagen and Trovagene during the time of the study. Please see the full study for a list of all other researchers’ relevant financial disclosures. Meijer reports speaker fees from GlaxoSmithKline, Menarini, Qiagen, Roche Diagnostics, Sanofi Pasteur-MSD/Merck and Seegene; consultant/advisory roles with Genticel, GlaxoSmithKline, Qiagen, Roche and Sanofi Pasteur-MSD/Merck; and minority shareholder roles with Dissay B.V. and Self-Screen B.V. Snijders reports a minority shareholder role with Self-Screen B.V.; speaker roles with Abbott, Gen-Probe, Qiagen, Roche Diagnostics and Seegene; and a consultant role with Crucell B.V.