A Long Way: History of the Prophylactic Papillomavirus Vaccine

For more than one and a half centuries, papillomaviruses have been recognized as causative agents for benign and malignant disease in humans as well as in a number of animal species [43]. It took more than five decades to provide sufficient evidence for the general acceptance of HPV as necessary cause for the development of anogenital cancer in humans. At the end of this long road of extensive studies on papillomaviruses by countless scientists worldwide there is finally a prophylactic papillomavirus vaccine at hand. Clearly, the scientific progress in vaccine development was hampered by the fact that papillomaviruses cannot be readily cultivated in vitro. In this review we will discuss the path that led to the introduction of the prophylactic vaccine to the public. Earliest reports about a putative infectious agent being involved in the development of cervical cancers came from observations made by the Italian physician Domenico Rigoni-Stern [51]. He noted that cancer of the womb is found most frequently among women in their fourth and fifth decade and he described behavioural risk factors for this cancer that are still being in the focus of modern epidemiology: age at first sexual intercourse and promiscuity. Despite an imprecise baseline of his study (Rigoni-Stern did not differentiate between cancer of the endometrial and cervical cancer) the link to cervical cancer was later confirmed by other