Human Papillomavirus Vaccines

Abstract

Human papillomaviruses (HPVs) include more than 100 viral types, with tropism for mucosa or skin. Infection with HPVs may become persistent, progress to precancerous lesions and eventually to invasion, causing cancers in a variety of sites, including the uterine cervix, vulva, vagina, penis, anus, oral cavity, oropharynx, and possibly the skin in patients with epidermodysplasia verruciformis. HPV infections are estimated to account for 5.2% of all cancers in the world, being responsible for 3% of mouth, 12% of oropharynx, 40% of penis, 40% of vulva/vagina, and virtually 100% of uterine cervix cancers. In particular, HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 are classified as group 1 carcinogens by the International Agency for Research on Cancer (IARC). Cervical cancer is the fourth most common cancer in women, and the seventh overall, with an estimated 528,000 new cases in 2012. Most (around 85%) of the global burden occurs in Low and Middle Income Countries (LMIC), where it accounts for almost 12% of all female cancers. There were an estimated 266,000 deaths from cervical cancer worldwide in 2012, comprising 7.5% of all female cancer deaths. Almost 9 out of 10 (87%) cervical cancer deaths occur in the LMIC regions. Mortality varies 18-fold among the different regions of the world, with rates ranging from less than 2 per 100,000 in Western Asia, Western Europe, and Australia/New Zealand to more than 20 per 100,000 in Melanesia (20.6), Middle (22.2) and Eastern (27.6) Africa. In addition to causing malignant cancers, HPV are also the cause of genital warts (GWs), histologically benign lesions that represent the most common sexually transmitted disease in many countries. Several million cases of GWs occur every year in the world in both females and males, with a peak incidence between 20 and 24 years of age for women, and between 25 and 29 years among men. HPVs are also responsible for a very rare but extremely debilitating disease, juvenile onset recurrent respiratory papillomatosis (JORRP), characterized by the growth of recurrent tumors in the respiratory tract, which results from a vertical transmission of HPV from mother to child. Virology studies have substantiated the link between genital condylomas and JORRP. HPV types 6 and 11, which are responsible for 80–90% of the condylomas, are responsible for nearly 100% of JORRP.