In addition to screening PSA testing for prostate cancer and screening mammography for breast cancer, the U.S. Preventive Services Task Force (USPSTF) also recommended changes in routine screening for cervical cancer. Again, their recommendation was for less screening, prolonging annual PAP smears to every three years for low to average risk women. Predictably, controversy ensued. All three tests were proven to diagnose potentially lethal cancers before symptoms appeared, and therefore, with early treatment, reduce the chances of these cancers from ever appearing (secondary prevention). So what’s not to like?
For reference, I turned to “The Emperor of All Maladies; A Biography of Cancer” by Siddhartha Mukherjee, M.D., published by Scribner, 2010. Part Four in this remarkable book is entitled: “Prevention is the Cure”. The saga of George Papanicolaou is chronicled and is worth reading (pp 286-291). Mukherjee then turns his attention to issues involving screening trials in general. “Screening trials in cancer are among the most slippery of all clinical trials-notoriously difficult to run, and notoriously susceptible to errors.” There are two main performance errors to consider:
- Overdiagnosis (false positives) meaning you test positive for cancer but you don’t have it. Not good for your emotional and physical wellbeing. Can lead to tests and treatments that are unnecessary and possibly harmful.
- Underdiagnosis (false negatives) meaning you test negative but really have cancer. Again, not nice. Over the years, I’ve had a not insignificant number of women state that their cancers were not detected on mammography initially and they, therefore, request an alternative screening modality.
Unfortunately, when researchers try to reduce the likelihood of false positives, the test in question can become too insensitive and result in more false negatives, and vice versa. The goal is to design a test with the highest sensitivity and specificity as possible, but achieving this can be difficult.
The USPSTF is currently examining these tests from another perspective, i.e., whether or not the test improves mortality. This criterion has to be distinguished from increased survival that can be flawed by lead time bias. If we are using increased survival as the endpoint of the study, some in the group screened by PAP smears when they are asymptomatic may develop cervical cancer a decade later and survive 5 more years. Some patients in the unscreened group develop their cancers ten years later, and also survive 5 years. Thus, the screened patients may appear to survive longer if lead time bias is not taken into account.
Certainly, we’re able to diagnose cancers when they are smaller and possibly curable with modern day treatments. But these screening tests give very little information about the biology of an individual patient’s cancer. When the topic of PAP smears and cervical cancers comes up, my mind focuses on “the Immortal Life of Henrietta Lacks” and her HeLa cells. I wrote a ‘Hela Cells’ blog post on this fascinating story several months ago. So when the author, Rebecca Skloot, was in San Diego two weeks ago, I made it a point to hear her speak. Would events have transpired differently now?
- “What if” no socioeconomic barriers to healthcare existed? No racism, poverty and lack of education. Regular PAP smears may have given her a better chance.
- “What if” it was recognized initially how aggressive her cancer was? She had a rare variant cervical cancer, an adenocarcinoma, which is known to be more aggressive than the more common squamous cell type. When she initially presented she was found to have a small tumor. Her physicians were surprised to see how rapidly Henrietta”s cancer recurred and spread after extensive surgery and radiation therapy.
- “What if” we knew more about her risk factors? We know the histology of her cancer indicated a more aggressive malignancy. We know that it is a sexually transmitted disease in “sexually active” young women, and that she had other STD’s.
- Then, maybe her disease could have been prevented with the HPV vaccine. When her cancer cells were analyzed for the human papilloma virus, they tested positive.
Hindsight is 20-20. But it is interesting to go back in time to see how much progress we’ve made and paths we need to pursue now.