Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy

Viruses, from the Latin "slime" or "poisonous juice" were not understood as unique entities until the 19th century. ¹ The major development that lead to understanding viruses occurred in 1884 when Chamberland created a filter with pores small enough to retain bacteria, yet large enough for viruses to pass through. ¹ A century later, in the 1950s, a variety of viral particles were documented by electron microscopy. ²

Papilloma virus was initially isolated from cottontail rabbits in 1933. ^{2, 3} In 1935 it was discovered that papillomas induced by papilloma virus had the potential to transform into malignant processes. ^{2, 4} Squamous cells that developed from human papilloma virus (HPV) lesions were noted in 1956. ⁵ The authors called these cells koilcytotic atypia or koilocytosis, meaning "hollow", from the Greek word koilos. ⁵ Before the invention of cloning techniques in the 1970s, investigation of HPV was difficult since the virus does not grow in culture. ⁶ Zur Hausen cloned the potentially malignant HPV 16 in the 1980s. ⁶ By the end of the 20th century, over 100 types of HPV were identified. ²

HPV is recognised as a public health problem for its role as a sexually transmitted disease and also as a critical factor in the pathogenesis of various cancers. HPV is a crucial element in the development of cervical cancer, the third most common malignancy in women. ⁷ The cause and effect relationship between HPV and cervical cancer is compelling. HPV DNA has been found in 90% of cervical cancer and 50% of vulvar cancer. ⁸ Fifty per cent of young, sexually active women are infected with HPV types that may promote the development of cancer. ⁹ In fact, HPV 16 and 18 have been classified as "carcinogenic" by the World Health Organisation International Agency for Research on Cancer. ⁷

CLINICAL PRESENTATION

HPV infection is initially asymptomatic ¹⁰ and transmission between people occurs before overt expression of the virus is seen or felt. Clinically, HPV infects the basal cells of the epithelium ¹¹ of skin and mucous membranes. ¹² Because HPV may affect sites where there are epithelial cells, ¹³ infections have been documented in the oral mucosa, oesophagus, larynx, trachea, conjunctiva, ¹⁴ as well as genital and anal areas. ¹² HPV...