Cervical Cancer Screening: Why do we do the things we do?

By Eva Martin, MD of Elm Tree Medical Inc.

Dr. George Papanicolau began working on a way to detect cancerous changes in the cells of the cervix in the 1920s, leading to the famous mainstay of cervical cancer screening- the “pap smear.” Fast-forward to 2016 and we have volumes of new knowledge about cervical cancer and screening methods. Gone are the days of the simple “annual pap,” now replaced by various combinations of tests at various intervals.  How did we get here? And where is here, exactly?

Drs. Lees, Erickson, and Huh provide us with a fantastic review article on the history of cervical cancer screening and evidence for our current practice in their article in the April 2016 Gray Journal.

The Pap Smear

Dr. Papanicolau teamed up with his colleague Dr. Herbert Traut and first published his work on the cervicovaginal smear in 1941. Yes- the “pap smear” could easily have been dubbed the “Traut smear.” Without any large randomized trials to back it up, the annual pap smear became the standard for cervical cancer screening. It’s a good thing- because proof that pap smear screening works came as the years rolled by.  In the 1950s to 1970s, when annual pap smears became routine practice in the United States, the rate of cervical cancer deaths fell by 3% every year. Before the pap smear, in the 1930’s, 36 per 100,000 women died from cervical cancer. When pap smears were routine practice, in the 1990s, that number fell to 7.2 per 100,000 women. Simply put, the reason we do pap smears is that history has told us that they save lives.

HPV Testing

In 1984 Dr. Harald zur Hausen made a tremendous discovery that earned him a Nobel Prize. He isolated a virus that could cause cancer- HPV. To be more specific- he isolated the high risk HPV types 16 and 18 that cause about 70% of all cervical cancer. Once we had knowledge of the causal link between the virus and the cancer, it only made sense that researchers would develop a way to test for the virus. In 1999, the FDA approved HPV testing, but not as a first line screening tool. Initially, HPV testing was only used to double-check after a woman had an abnormal pap smear result. Five years later, in 2004, the great decision-makers in OBGYN decided that HPV testing could be used with the pap smear for women 30 years of age and older.

Now, the standard recommendation is “co-testing” every 5 years for women aged 30 and older. How did we get from annual pap smears for everyone to co-testing every five years? First, let’s tackle women under the age of 30.

Under age 30

The first obvious question is, when do we start cervical cancer screening? The answer now is, 21 years of age. What about the 19-year-olds with HPV? Because they are much, much more likely to clear the infection than to develop cervical cancer. About 28% of US women under age 21 have HPV, but only 14 will develop invasive cervical cancer. Furthermore, even if we did screen all the teens in America, the number of girls who get invasive cervical cancer would be the same. Data from the 1970’s to today shows that screening these adolescents didn’t help, but the interventions that the screening caused- like colposcopy and surgical excision- could hurt them. For instance, if a young women undergoes a procedure to remove part of her cervix, she is at increased risk of having a preterm birth in a later pregnancy. Preterm birth is the leading cause of infant mortality and morbidity in the United States.

What about the 21 to 29-year-olds? Millenials have every right to be confused on this one- the recommendations have changed throughout the early 2000s and very well could change again. In 2012, all of the big OBGYN organizations finally agreed on a singular recommendation- pap smear every 3 years. Like teens, many of them have HPV (up to 54%), but cervical cancer remains very rare. Why not two years? A computer-modeling study showed that two year screening and three year screening had the same death rate. Why not four years? A large Scandinavian study showed an increased risk of precancer in women who waited longer than three years between their pap smears.

Age 30 to 65

If you are in this age group, you get both HPV testing and pap smears when you visit your GYN, but you only need it every 5 years, according to the latest guidelines. Women in this age group are less likely than younger women to clear an HPV infection, so adding co-testing increases the ability to detect precancers. By what stroke of luck did they get a reprieve from repeat testing for 5 years if everything was normal? A European study in 2008 showed that women with a normal pap smear had a 0.17% risk of developing pre-cancer 3 years later. Women with a negative HPV test had a 0.17% risk of developing pre-cancer 5 years later. So, the Power That Be decided that, since the risks are equal at 5 years when you add that negative HPV test to the equation, it is safe to wait 5 years between co-testing. Of course, if a woman only gets a pap smear and no co-test, then the interval is still 3 years. And- if the results are abnormal, all of these recommendations go out the window!

Over Age 65

If a woman has “previous adequate negative screening,” then she is home free at age 65. One of the interesting and little known facts about the cervix is that it changes with age. By 65, the area that is most likely to become cancer is smaller, making HPV infection less likely. Computer decision-modeling has shown that continuing screening won’t prevent much cancer, but it would cause doctor to perform a lot of unnecessary and painful procedures.

The Future

The first big question for the future is- why are we even doing pap smears? Do they add anything now that we have HPV testing? The answer is, for now, yes, they add information that HPV testing does not provide. However, in the future, we may see HPV-testing alone as the first line screening test. HPV testing can increase our ability to find new pre-cancers, but without the information from the pap smear, it leads to more false-positives and thus more unnecessary procedures.

One topic we haven’t covered at all is the HPV vaccine. Shouldn’t this vaccine totally change the way our screening tests function? Theoretically, yes. HPV testing may become even more important. However, uptake of the vaccine has been low in the United States. For now, the push must be towards increasing vaccination rates for boys and girls to prevent cervical cancer (and other cancers) before they start.