Human Papillomavirus (HPV) refers to a common group of over 200 distinct viruses. While many types cause no noticeable symptoms, some can lead to warts or, in specific cases, certain cancers. This widespread viral infection has a long history, from its ancient evolutionary origins to its modern scientific understanding and the development of preventive measures.
Earliest Traces of Human Papillomaviruses
The history of papillomaviruses, the family to which HPV belongs, stretches back millions of years. Phylogenetic studies suggest these viruses have co-evolved with their vertebrate hosts for as long as 500 million years, with their evolution closely linked to the diversification of mammals. Cancer-causing human papillomaviruses are estimated to have diverged from common ancestors approximately half a million years ago, a timeframe aligning with the separation of archaic Neanderthals and modern Homo sapiens. This implies HPVs have been present in human populations for a very long time, adapting alongside their hosts.
Evidence from ancient DNA provides further insight. Papillomavirus DNA has been found in samples as old as 27,000 years, indicating the virus’s presence in past ecosystems. HPV DNA has also been identified in preserved human remains, including a 16th-century mummy with traces of HPV18. These findings suggest certain HPV variants may have been transmitted to modern humans through interbreeding with archaic hominins like Neanderthals, influencing the current global distribution of some HPV types.
The Discovery of HPV and Its Diseases
Early observations of HPV-related conditions, particularly warts, date back to ancient Greek and Roman medical literature. The infectious nature of warts became more formally recognized in the late 19th and early 20th centuries. In 1891, British physician Joseph Payne reported that common warts were contagious. Giuseppe Ciuffo, an Italian scientist, further demonstrated the viral nature of warts in 1907 by showing that a cell-free filtrate could transmit them.
A significant step in modern medical recognition came from Georgios Papanikolaou, a Greek physician. In 1928, he published findings on the cytopathology of the human female genital tract, describing cellular changes that could differentiate between healthy and malignant cells in cervical smears. This work led to the development of the Pap smear, which became an important tool for detecting precancerous cervical lesions and was widely recognized by 1941.
Understanding HPV’s Role in Cancer
Despite early suspicions, the definitive link between HPV and cancer was a scientific breakthrough of the latter half of the 20th century. For decades, herpes simplex virus type 2 (HSV-2) was mistakenly considered a primary cause of cervical cancer. However, German virologist Harald zur Hausen challenged this theory, hypothesizing in 1976 that human papillomaviruses were the true cause. His research involved searching for HPV DNA in cervical tumor samples.
Zur Hausen’s team made a key discovery in the early 1980s by identifying specific HPV types, HPV16 (1983) and HPV18 (1984), within cervical cancer biopsies. They demonstrated that these types were consistently present in a majority of cervical cancers worldwide. This work, which included showing how viral genes integrate into host cell DNA, definitively established HPV as the primary cause of cervical cancer. His discoveries also led to the understanding that HPV could cause other cancers, including those of the anus, vulva, vagina, penis, and oropharynx, for which he was awarded the Nobel Prize in Physiology or Medicine in 2008.
Global Recognition and Prevention Efforts
The understanding of HPV’s role in cancer spurred global public health action. The Pap smear, initially developed in the late 1920s and gaining widespread adoption by the 1940s and 1950s, became a cornerstone of cervical cancer screening programs. This screening method significantly reduced cervical cancer mortality rates in many countries.
Building on the definitive link between HPV and cancer, scientists developed a vaccine. In the early 1990s, Professors Ian Frazer and Jian Zhou developed “virus-like particles” (VLPs) that mimic HPV’s outer shell but do not contain viral DNA, making them incapable of causing infection. This innovation paved the way for the first HPV vaccines. The United States Food and Drug Administration (FDA) approved Gardasil, the first HPV vaccine, in 2006, followed by Cervarix in 2007, and later Gardasil 9 in 2014, which protects against more HPV types. These vaccines represent an important advancement in cancer prevention, with many countries integrating HPV vaccination into their routine immunization schedules.