Examining the Evidence
Should primary cervical cancer screening of women 30 years and older include HPV testing?
Sankaranarayanan and colleagues report the long-term follow-up of 130,000 women in rural India, who were randomized in 1999 to receive a single screen using one of the following:
- conventional Pap test
- HPV test (Hybrid Capture 2)
- visual inspection of the cervix with acetic acid (VIA)
- no screen (the current standard in India).
Within 8 years of a single HPV test, the incidence of both advanced cervical cancer and cervical cancer mortality declined significantly. In contrast, neither a single Pap test nor a single VIA had a substantial impact on either the incidence of advanced cervical cancer or mortality. Not a single cancer occurred among the 90% of women who tested negative for HPV at enrollment.
Properly timed, the HPV test can avert more advanced cervical cancers and deaths in developing countries than other screening methods
The burden of cervical cancer is shouldered largely by the developing world, where an estimated 80% of the nearly 500,000 cervical cancers occur annually, and where screening has been too costly and complicated to instigate. This study provides the first evidence that a single screen with an HPV test, best performed 15 to 20 years after the median age of first intercourse, would save more lives than other options and may be affordable.
A low-cost, simple, and highly sensitive HPV test (careHPV test) has been developed, with financial backing from the Bill and Melinda Gates Foundation, through the Alliance for Cervical Cancer Prevention. This test provides results within 3 hours and is now being used in demonstration projects in several countries. This appears to offer a way to prevent thousands of deaths from cervical cancer worldwide.
In the United States, cotesting is more effective—and affordable—than the Pap test alone
Castle and associates provide in-depth information on cotesting in women 30 years and older using both the Pap and HPV tests in primary screening in a US setting.
A major concern about cotesting has been that the addition of the HPV test might burden the system with too many positive results, but this study demonstrates otherwise. In the general population of women of this age, the number of HPV-positive results is not burdensome.
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In 2003, Kaiser Permanente Northern California instigated cotesting of all women 30 years and older who elected this screening option. Over the next 4 years, nearly 813,000 cotests were performed on more than 580,000 women (median age, 44 years). Overall, 6.27% tested positive for high-risk HPV using Hybrid Capture 2. Among the 93% of women who tested negative for high-risk HPV, the risk of missed precancer and cancer was extremely low, because HPV testing detects most of the 25% to 50% of these lesions missed by a single Pap test.
The authors point out that, for the 90% of women who tested negative on both the Pap and HPV tests, the risk of incipient precancer or cancer is likely to be very low for the next 10 years or so. Therefore, most women who undergo cotesting could be safely screened at 3-year intervals, and those screened more irregularly would likely be better protected than women screened by cytology alone. Extending the interval makes cotesting more cost-effective and has other benefits, as well.
Rate of HPV-positive findings varied by age
Among women 30 years of age and older, there is some variation in the rate of HPV-positive results. In this study, HPV-positive results were found in:
- 10.8% of women 30 to 34 years old
- 8.0% of women 35 to 39
- 6.3% of women 40 to 44
- 4.9% of women 45 to 49
- 4.3% of women 50 to 54
- 3.9% of women 55 to 59
- 3.7% of women 60 to 69
- 5.3% of women 80 years and older.
The highest rate of HPV was found among women in their 30s. This is the same age group that has the highest rate of high-grade precancer (cervical intraepithelial neoplasia grade 2,3) in the Kaiser health system.
Findings are in line with other studies
The study by Castle and colleagues is the largest general-population screening investigation of cotesting published so far. The rate of HPV-positive and Pap-negative findings was 3.99% for the group of women 30 years and older, which is right on target with the 3.7% rate for cotesting demonstrated in the Netherlands and the 4% rate reported in a US survey by the College of American Pathologists. All women of this age in the Kaiser system were given the option of continuing to get an annual Pap or switching to cotesting every 3 years; 91.6% chose the cotesting option.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
More and more, data point to cotesting as the screen of choice for women 30 years and older, with the screening interval extended to 3 years for any patient who tests negative on both HPV and Pap tests.—J. THOMAS COX, MD