Cervical Cancer - History

History

• 400 BCE - Hippocrates: cervical cancer incurable
• 1925 - Hinselmann: invented colposcope
• 1928 - Papanicolaou: developed Papanicolaou technique
• 1941 - Papanicolaou and Trout: Pap smear screening
• 1946 - Ayer: Aylesbury spatula to scrape the cervix, collecting sample for Pap smear
• 1951 - First successful in-vitro cell line, HeLa, derived from biopsy of cervical cancer of Henrietta Lacks
• 1976 - Zur Hausen and Gisam: found HPV DNA in cervical cancer and warts
• 1988 - Bethesda System for reporting Pap results developed
• 2006 - First HPV vaccine FDA approved

Epidemiologists working in the early 20th century noted that cervical cancer behaved like a sexually transmitted disease. In summary:

1. Cervical cancer was common in female sex workers.
2. It was rare in nuns, except for those who had been sexually active before entering the convent. (Rigoni in 1841)
3. It was more common in the second wives of men whose first wives had died from cervical cancer.
4. It was rare in Jewish women.
5. In 1935, Syverton and Berry discovered a relationship between RPV (Rabbit Papillomavirus) and skin cancer in rabbits. (HPV is species-specific and therefore cannot be transmitted to rabbits)

This led to the suspicion that cervical cancer could be caused by a sexually transmitted agent. Initial research in the 1940s and 1950s put the blame on smegma (e.g. Heins et al. 1958). During the 1960s and 1970s it was suspected that infection with herpes simplex virus was the cause of the disease. In summary, HSV was seen as a likely cause because it is known to survive in the female reproductive tract, to be transmitted sexually in a way compatible with known risk factors, such as promiscuity and low socioeconomic status. Herpes viruses were also implicated in other malignant diseases, including Burkitt's lymphoma, Nasopharyngeal carcinoma, Marek's disease and the Lucké renal adenocarcinoma. HSV was recovered from cervical tumour cells.

A description of human papillomavirus (HPV) by electron microscopy was given in 1949, and HPV-DNA was identified in 1963. It was not until the 1980s that HPV was identified in cervical cancer tissue. It has since been demonstrated that HPV is implicated in virtually all cervical cancers. Specific viral subtypes implicated are HPV 16, 18, 31, 45 and others.

In work that was initiated in the mid 1980s, the HPV vaccine was developed, in parallel, by researchers at Georgetown University Medical Center, the University of Rochester, the University of Queensland in Australia, and the U.S. National Cancer Institute. In 2006, the U.S. Food and Drug Administration (FDA) approved the first preventive HPV vaccine, marketed by Merck & Co. under the trade name Gardasil.