Unclear if HPV testing prevented more cervical cancer
- by Judy George, Contributing Writer, MedPage TodayJune 22, 2017
Human papillomavirus (HPV) tests resulted in faster and more complete diagnosis of precancerous lesions than Pap smears alone, but also led to more biopsies and surgical treatment of low-grade lesions, according to a new analysis of the New Mexico HPV Pap Registry published in JAMA Oncology.
HPV screening led to a nonsignificant 15.8% increase in detecting overall cervical intraepithelial neoplasia grade 3 or worse (CIN3+) lesions, and did so much more quickly than Pap smears alone, in a median time of 103 versus 393 days. It also detected significantly more of the less severe CIN1 and CIN2 lesions, and resulted in 55.8% more biopsies and a 20% higher rate of loop electrosurgical excision procedures (LEEP).
"This study is the first comprehensive evaluation to date of the influence of HPV testing on the long-term outcome associated with ASC-US (atypical squamous cells of undetermined significance) cytology," wrote Cosette Wheeler, PhD, of the University of New Mexico Health Sciences Center in Albuquerque, and colleagues.
The Wheeler group analyzed the clinical records of 457,317 women whose average age was 39.8 (±12.5 years) from New Mexico's population-based cervical screening register from 2008 to 2012, linking Pap smears and HPV tests to pathology reports.
The primary objective was to study 5-year outcomes after a Pap smear, with versus without HPV testing. Of the 457,317 women, 20,677 (4.5%) had an abnormal Pap smear result, and 16,648 of the 20,677 -- 80.5% -- had HPV testing.
Over 5 years, HPV screening detected CIN3+ lesions (adenocarcinoma in situ or cancer) in 2.49% of women, compared to a 2.15% detection rate in women who did not have HPV testing (RR 1.16, 95% CI, 0.92-1.45, P=0.23). HPV triage made a difference detecting high-grade lesions especially during the first year of follow-up, when the detection rate was 1.49% versus 0.93% (RR 1.60, 95% CI, 1.14-2.24, P=0.004).
By year 5, however, the relative risk dropped and the absolute difference decreased from 0.56% to 0.34%, indicating that most CIN3+ lesions were persistent.
Among those tested for HPV, virtually all CIN2 and CIN3+ disease occurred in HPV-positive women. The RRs for this group always were above 10, except CIN3+ in women ages 50 to 64, where it was 7.64.
HPV screening also detected CIN1 lesions in 11.6% of women, compared to a 6.5% detection rate in women who were not screened for HPV (RR 1.76, 95% CI 1.56-2.00, P<0.001). This increase was similar across age groups (P=0.32). Among those tested for HPV, CIN1 lesions were much more common in women who were HPV-positive (24.3% versus 2.7% after 5 years; RR 9.11, 95% CI, 8.01-10.36, P<0.001), and was detected in a median time of 61 versus 582 days (P<0.001).
"This study shows that knowing a woman's HPV status can help determine her likelihood of needing additional procedures and prioritize immediate treatment and medical resources to the women who need them most," said Jack Cuzick, PhD, director of the Wolfson Institute of Preventive Medicine at Queen Mary University of London, who was part of the research team.
In an accompanying editorial, Chris Meijer, MD, PhD, and Peter Snijders, PhD, of the pathology department at VU University Medical Center in Amsterdam, pointed out that although HPV triage is effective at detecting cervical disease in a shorter time, it comes at the cost of more biopsies and LEEPs.
It's unclear whether HPV testing prevented more cervical cancer or whether the reduced time balances the risks of overtreatment, they noted. Among young women especially, an HPV-positive test may stem from a transient HPV infection, and CIN1 and a subset of CIN2 lesions often regress spontaneously without progressing to cervical cancer. CIN3 lesions -- the most advanced cervical cancer precursors -- may persist for more than 2 decades before cervical cancer eventually develops.
"The HPV triage strategy [used in this study] detects more CIN1 and CIN2 than the algorithm without HPV testing and at present triggers considerable overtreatment of many women of reproductive age who will never develop cervical cancer," they wrote. "These unnecessary treatments are associated with a significant cervical morbidity, including preterm birth, perinatal mortality, and low birth weight."
Other triage tests also should be considered, they wrote, adding that the latest host gene methylation assays perform well against other options and should have a low cancer risk for test-negative women.
Because this was an observational study, HPV testing was not randomized in this research. It is possible women not tested for HPV had a different disease risk, or their clinicians used a different follow-up strategy after Pap smears. Clinics in rural areas were less likely to use HPV testing, the researchers noted, and even in urban areas, public health clinics and some federally-qualified health centers had almost no HPV testing during the study period.
This study was funded by a grant from the Population-Based Research Optimizing Screening Through Personalized Regimens (PROSPR) consortium, which is funded by the U.S. National Cancer Institute.
Wheeler reported relationships with the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, GSK, Merck, and Roche Molecular Systems. Dr. Cuzick disclosed relationships with Abbott, Becton Dickinson, Cepheid, Merck, Hologic, OncoHealth, Qiagen, and Trovagene. The research team reported no other relationships.
Meijer and Snijders are minority shareholders of Self-Screen B.V., a spin-off company of VU University Medical Center with patents on human papillomavirus testing and methylation markers for cervical screening. They also disclosed relationships with GSK, Qiagen, Sanofi Pasteur-MSD/Merck, Roche Diagnostics, Menarini, Seegene, Abbott, Genticel, Crucell B.V., Diassay B.V., and Delphi Biosciences.
- Reviewed by F. Perry Wilson, MD, MSCEAssistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner