The Pap smear has been available for many years. Why is testing for human papillomavirus (HPV) now part of the testing process?
Question: The Pap smear has been available for many years. Why is testing for human papillomavirus (HPV) now part of the testing process?
Our Response: Ever since Aurel Babes in Romania and George Papanicolaou in 1928 linked abnormal cells to cancer, cervical cancer deaths have been on the decline. Yet, most recent data from the Centers for Disease Control and Prevention (CDC) predicted that in 2016, 1,685,210 new cases of cervical cancer and 595,190 deaths would occur.
Like most cancers, cervical cancer was assumed to originate from multiple biologic causes. However, in 1983, Harold zur Hausen isolated the HPV 16 strain from cervical cancer cells, thus redirecting international research toward “the first human cancer with a single necessary cause.”
The relationship of cervical cytology to HPV status, however, can be confusing. Adult cells on the surface of the cervix, when collected by the Pap smear, start normally as small stem cells along the basement membrane, a structure deeper in the cervical tissue. Some of these stem cells multiply and divide as they mature, migrating toward the surface. During this maturation process, certain strains of HPV, if present, are capable of inserting their DNA into these dividing cells, thus altering the cell’s genetic code.
Twelve HPV high-risk strains linked to cervical cancer have been identified. Fortunately, only high-risk strains like HPV 16 (which accounts for over 50% of cervical cancers) and HPV 18 (which accounts for 10% to 20% of cervical cancers) express the oncogenes E6 and E7. E6 inactivates tumor suppressor P53, which normally codes for a protein that regulates the cell cycle. E7 disrupts formation of transcription factors normally involved in synthesizing DNA. While rare, persistent HPV-infected cells risk undergoing mutations that over ten to 20 years can develop into cervical cancer.
Today, the ongoing debate for care of women over 25 is whether HPV testing should back up cervical cell cytology or be administered as a first-line screen for risk of cervical cancer.
James Woods | 10/3/2019
