"I had been getting Pap smears every year or two since I was 17," says Kira. "But I didn't really know much about the test or what it was looking for. I even had an abnormal result once or twice, but the only thing that meant was that I needed a follow-up. A year ago, though, when I changed gynecologists, my new health care provider said my records indicated I might have had a sexually transmitted infection called HPV. I was floored. I feel like I had a right to know. Why didn't anyone tell me?"

Like Kira, most women accept the Pap smear as an obligatory ritual. They schedule the visit, put their feet in the stirrups, hope the speculum's not too cold, and wait for the results. No news is good news. Out of sight, out of mind.

In reality, however, no news is not necessarily good news, because, as in Kira's case, some health care professionals don't disclose to their patients the risk factors for cervical disease-or, in some cases, do not explain the Pap test results thoroughly. And what's out of sight is not necessarily unimportant. The sexually transmitted human papillomavirus (HPV), often an invisible infection, has now been closely linked with cervical cancer. Future strategies for early detection and management of cervical disease, therefore, may hinge on efforts to detect HPV rather than waiting for the damage it sometimes causes.

How the Standard Pap Test Works

The Pap smear is named after physician George Papanicolaou, who introduced the technique in 1949 with the goal of detecting signs of cancer in the cervix through a simple and inexpensive procedure.

In the standard Pap test, a healthcare provider collects from the cervix a small sample of cells which are then smeared onto a glass slide (hence the term "smear"). The slide is sent to a medical laboratory where a cytotechnologist--someone with training in recognizing the appearance of many different types of cells--views it under high magnification. The goal is to see whether, among thousands of unremarkable-looking cells, there lurk any with the telltale features of malignancy or viral infection. Studies suggest about 20% of Pap tests give "false negative" results--meaning an abnormality is overlooked. This is one reason to have repeated Pap screening at regular intervals. Many health agencies recommend a Pap test every year beginning at age 18 or at the onset of sexual activity, though some recommend an interval of every two or three years.

From a historical perspective, the Pap test has proved to be a major public health innovation, dramatically reducing the incidence of cervical cancer. Papanicolaou's technique, however, was designed at a time when the root cause of cervical cancer was unknown. By the 1970s, a major body of research suggested that cervical abnormalities were closely linked with sexual activity and perhaps with specific sexually transmitted infections. A decade later, scientists had narrowed their search principally to one infectious agent: human papillomavirus (HPV).

HPV and Cervical Infection

Some of HPV's more than 100 types cause simple hand warts or plantar warts on the feet. Others-about one-third of HPV types--are implicated in genital warts or cervical abnormalities. Genital HPV is incredibly common, infecting a majority of sexually active adults at some point. It is a benign infection in the vast majority of cases, but some of the warning signs indicated by a Pap test are in fact signals that certain types of HPV are present.

While the Pap smear still plays an important role in a woman's health care, researchers have developed the ability to identify the DNA of many HPV types, and new diagnostic tests can help pinpoint the presence of HPV types implicated in cervical disease.

Outside of the research laboratory, the major HPV DNA test currently approved by the Food and Drug Administration is called Hybrid Capture II. It can detect a number of common HPV types in Pap smear samples or cervical biopsy specimens. Hybrid Capture II has remarkable accuracy in detecting up to 13 high-risk HPV types and a number of low-risk types. The test is machine-readable, thus reducing human error, and can be run directly on some Pap smear samples.

Despite its potential merits, HPV typing is not yet a routine part of gynecologic care. Experts are still investigating whether the addition of HPV tests will actually lower the costs of screening and treatment or ultimately reduce the incidence of cervical cancer. Hybrid Capture II is currently approved by the FDA for use in cases where a Pap test result is unclear--"of unknown significance." Studies have shown that a significant percentage of all unclear or "equivocal" results are related to HPV. Thus, when applied to this kind of sample, the HPV test can determine whether low-risk or high-risk HPV types are present. If high-risk types are found, the patient can be referred for tests such as colposcopy and biopsy, which are more expensive and invasive; if not, she can simply be followed with repeat Pap smears.

Does this test require an extra office visit? Not necessarily. Pap tests done with a new collection system called ThinPrep(R) create a sample that can also be used for HPV typing tests, so one visit offers the potential for two different tests. But HPV testing can also be performed with a cervical specimen obtained independently from the Pap smear, either from a special swab or from a biopsy.

To put matters in perspective, it's critical to remember that while HPV infection that affects tens of millions of American adults, it usually resolves without creating medical problems. In cases where Pap tests show cervical abnormalities, however, new technologies may be an important tool for getting much-needed answers about the cause of the trouble.