Trade-offs Favor HPV Test for Primary Cervical-Cancer Screen

Boston, MA

For cervical-cancer screening, human papillomavirus DNA tests should be given primacy over cytology to reduce unnecessary colposcopies without increasing cancer risk, researchers here said.

HPV DNA testing before cytologic triage testing would cut excessive colposcopies by 45% compared with the recommended strategy of cytologic testing followed by HPV triage testing, found Natasha K. Stout, Ph.D., of the Harvard School of Public Health, and colleagues.

Lifetime cancer risk varied little between screening strategies in their comparative analysis reported in the Sept. 22 issue of the Archives of Internal Medicine.

If all women ages 18 to 70 followed the DNA testing-first strategy, more than 300,000 unnecessary diagnostic procedures would be prevented annually in the U.S., the researchers said. Guidelines from the American College of Obstetricians and Gynecologists and the U.S. Preventive Services Task Force recommend cervical-cancer screening with a Pap smear followed by HPV DNA testing for women with abnormal or unclear findings

"How best to capitalize on the enhanced sensitivity of HPV DNA testing while minimizing false-positive results from its lower specificity is an important question to be addressed in upcoming screening guidelines," they wrote.

These trade-offs have become increasingly important as the risk of cervical cancer has dropped because of successful secondary prevention and the availability of new technologies, Dr. Stout's group said.

If the newly available HPV vaccine is as effective long term as expected, "the marginal health benefit from screening will be even smaller, potentially accentuating trade-offs in risks among strategies for some women," they noted.

The investigators simulated clinical outcomes for a million women using a computer model of cervical cancer in the United States.

Across the strategies modeled, referrals to colposcopy and further diagnostic workups expected over 10 years of screening ranged three-fold. Screening with combined Pap smear and HPV testing had the most referrals; HPV testing followed by cytologic triage testing led to the fewest.

Comparing the strategies, the findings for a representative group of 1,000 20-year-old women undergoing annual screening for 10 years were:

The researchers noted that more than 95% of referrals to colposcopy were for false-positive findings or unnecessarily performed on healthy women or those with cervical intraepithelial neoplasia (CIN) type 1, which often resolve without treatment.

On a population level, screening all women ages 18 to 70 in the U.S. with a Pap smear every three years followed by HPV triage testing as recommended in current guidelines would result in more than a million excessive colposcopies annually.

By comparison, putting HPV testing first would cut unnecessary procedures to 0.7 million, whereas combined cytologic and HPV testing dramatically increased this number to four million.

However, all the strategies appeared similarly effective at picking up cervical cancer.

The diagnostic rates of CIN types 2 or 3 ranged from five to seven cases per 1,000 women age 20 over 10 years of screening and from six to nine cases for a similar group of women initially age 40.

Lifetime cervical cancer risk ranged from 0.23% screened annually with combination cytologic and HPV testing to 1.02% for those screened every five years with conventional cytological screening.

The effect on life expectancy was even smaller because survival rates are high for cervical cancer detected in the early stages, Dr. Stout's group noted.

The impact on quality of life across ages and screening frequencies was worst with the combination screening approach because the potential negative effect of an abnormal finding or colposcopy outweighed the small reduction in lifetime cervical cancer risk.

The researchers also noted that primary HPV testing reduced quality of life because of the higher frequency of positive screening test results, but the lower likelihood for colposcopy offset the potential disutility compared with primary cytology-based strategies.

But because of the prevalence of high-risk HPV infection in women ages 30 and younger, cytologic test-based strategies may be better in this age group to minimize excessive diagnostic workups and HPV-positive results on the initial screening test, the researchers added.

"For women who experience short-term anxiety around screening and diagnostic workup, quality of life could be an important criterion for decision making if several screening options associated with similar cancer risk reduction are available," they concluded.

The investigators cautioned that the modeling approach used in the study was limited by the data and assumptions that went into developing the model. They also acknowledged that the analysis could not address important factors that go into women's screening decisions, such as peace of mind from diagnostic resolution.

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