It may be safe for women to extend intervals for cervical cancer screening to every 5 years or longer if screening results are consistently negative.
New findings, published online November 27 in Annals of Internal Medicine, show that there is a substantial decline in cervical cancer risk after one or more negative cotests with human papillomavirus (HPV) and cytology screening.
The results, which come from a follow-up of nearly 1 million women, show that the risk for invasive cervical cancer and cervical intraepithelial neoplasia of grade 3 or higher (≥CIN3) declined with each round of cotesting. The absolute decrease in risks was greater between the first and second round than between the second and third cotests, the authors report.
Changes in Screening Guidelines
Guidelines for cervical cancer screening have been in flux, especially with the advent of the HPV vaccine. For example, in its updated 2015 guidelines, the American College of Obstetricians and Gynecologists (ACOG) says that the HPV test can be considered an alternative to current cytology-based cancer in women aged 25 years and older. However, the ACOG still recommends cytology testing alone every 3 years and notes that cotesting with cytology and HPV testing every 5 years is preferred.
The US Preventive Services Task Force has also issued new draft guidelines in which testing for high-risk HPV strains alone is recommended as an alternative to cytology alone beginning at age 30 years. Cotesting is no longer recommended.
The authors of the new study, led by Philip Castle, PhD, MPH, of the Albert Einstein College of Medicine, New York City, note that experience with strategies incorporating HPV testing has been limited. In addition, much of the published evidence on HPV-based screening is based on a single round of cervical cancer screening.
Greatest Effect With First Test
In the latest study, Dr Castle and colleagues reviewed data for 990,013 women who underwent cotesting from 2003 to 2014 in the Kaiser Permanente Northern California integrated healthcare system to evaluate cervical cancer risk in routine practice after successive negative screening cotests.
They found that overall, an increase in the number of negative cotests was associated with a steadily decreasing risk for future cancer or ≥CIN3, with the first negative cotest having the greatest impact on risk reduction.
Importantly, within any given cotesting round, “the reassurance against cancer and cancer risk were similar for an HPV result alone, regardless of cytology results, and an HPV/Cyto co-test result,” the authors note.
With regard to HPV alone, the 5-year risk for invasive cervical cancer after a negative HPV test decreased from 0.0092% (9.2 per 100,000) for the first negative result (no preceding negative cotests) to 0.0015% (1.5 per 100,000) for an HPV negative result on the third cotest after two negative cotests.
Similarly, the 3-year risk for invasive cervical cancer following a negative HPV result decreased from 0.0081% (8.1 per 100 000) for the first test to 0.0015% (1.5 per 100 000) for a negative HPV result on the third cotest after 2 negative cotests.
In comparison, the 3-year cancer risk after a negative cytology test declined from 0.0140% (14 per 100 000) for the first result to 0.0023% (2.3 per 100 000) for a negative result on the third cotest after two negative cotests.
The 3- and 5-year ≥CIN3 risks from the first, second, and third cotests followed patterns that were similar to those of invasive cervical cancer. The 5-year ≥CIN3 risks decreased after each successive negative cotest screening round (0.098%, 0.052%, and 0.035%, respectively) as did the 3-year risk (0.070%, 0.036%, 0.020%).
The 3-year ≥CIN3 risk following a negative HPV test decreased after successive testing, from 0.085% for the first cotest to 0.024% for the third. The risk after a negative cytology test declined from 0.199% to 0.043%.
Stand-alone HPV vs Cotest
In an accompanying editorial, Guglielmo Ronco, MD, PhD, of the City of Health and Science Turin, Italy, and Silvia Franceschi, MD, PhD, of the International Agency for Research on Cancer Lyon, France, note that the current study confirms that at the first cotest, the risk for cancer among women with a negative HPV test is only slightly higher than the risk for those with negative cotest results. The risk decreases further after the second negative HPV cotest and disappears after the third.
They point that that it is “important to recognize that the invasive cervical cancer cases detected in women with HPV-/Cyto+ results” in the study by Dr Castle and colleagues do not exactly correspond to those that would have occurred after stand-alone HPV testing, because these were cases that were not prevented by knowledge of cytologic abnormalities.
“The most plausible reason for failure to prevent them is that invasive cervical cancer was already present when cytologic abnormalities were detected in exfoliated cervical cells,” the editorialists write.
The study confirms that “the gain in sensitivity with co-testing over standalone HPV is minimal for ≥CIN3,” say the editorialists.
“Of importance, co-testing leads to a substantial number of unnecessary colposcopies and biopsies, and perhaps to overtreatment,” they note.
Dr Castle was supported in part by an Intergovernmental Personnel Act assignment from the National Institutes of Health/National Cancer Institute. He received cervical screening tests and diagnostics from Roche, BD Biosciences, Cepheid, and Arbor Vita at reduced or no cost for research. Dr Castle’s coauthors are employed by the National Cancer Institute. Editorialists Dr Ronco and Dr Franceschi have disclosed no relevant financial relationships.
Ann Intern Med. Published online November 27, 2017. Abstract, Editorial
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