E6, E7, and HPV, oh my!

July 22 2015

Some women may have noticed that in the past 2 years, their primary doctors or GYNs no longer check pap smear annually. Why not? To answer that question, we must understand 1) what is a pap smear and 2) the natural history of cervical cancer.
During a pap smear, a sample of cervical cells are picked up with a small brush or "spatula". These cells are sent to the pathologist who stains them with certain dyes which allow visualization of the cells via the microscope. (The images are actually quite beaufiul - do a image search for "pap smear histology".) Based on certain features of the cells, the pathologist decides whether the cells are normal or abnormal. If abnormal, the pathologist decides on exactly how abnormal - from cells of "uncertain significance" to cancerous cells.  Thus, one of the goals of pap smears is to detect pre-cancerous cells and early stage cervical cancer.
The development of cervical cancer is a stepwise progression from pre-cancerous lesions (CIN 1 --> CIN 2 --> CIN 3) to invasive cancer. This process usually takes many years. Like all cancer, it starts with one cell that had mutated enough to allow it 1) to escape death and 2) to grow unrestricted. How did this cervcal cell get mutated? Epidemiology research have shown that almost all patients with cervical cancer also test positive to HPV (human papillomavirus). The most common types of HPV are labelled "high risk" types. HPV 16 accounts for 55-60% of the cases. The second runner up is HPV 18 which accounts for 10-15%. The current theory is that HPV infects cervical cells and can produce oncoproteins which can suppress the cell's own proteins that are responsible for regulating cell growth.
Not everyone who has HPV will develop cervical cancer or even pre-cancerous cells. In fact, 90% of HPV infections resolve because our immune system can fight off the HPV infection. This is why sometimes patients can have abnormal cells on pap smears that will no longer be present with the next pap smear. Persistent HPV infection is worrisome for high grade pre-cancerous lesions that have higher risks of developing into cervical cancer.  Given the close association of HPV with cervical cancer, testing patients for HPV infection along with pap smears can better predict who is at higher risk of developing cervical cancer. Given that most HPV infections are transient and that cervical cancer takes years to develop, the American Society of Colposcopy and Cervical Pathology has recommended that women should not be screened annually with pap smear. Guidelines now recommend screening intervals that change based the patient's age as well as prior pap smear and HPV results.
I hope you found that interesting and enlightening! I am an OB/GYN who firmly believes in the power of patient education and medical literacy. If you are a scientist and/or dreamer, I would like your help to change the way we perform surgery. For hundreds of years, surgery is performed with the scalpel (in its many permutations). Wouldn't it be amazing if we could develop a targeted cellular or molecular based approach where the patient ingests or is injected with a compound that digests whatever tissue (gallbladder, uterus, cancer, etc) that needs to be removed? That would be the ultimate "non-invasive" surgery!
Live long and prosper,

Chensi Ouyang
[email protected]
New York

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