Human papillomaviruses (HPV) are DNA tumor vi­ruses that are species specific. They infect cutaneous and mucous epithelia through cuts or abrasions and induce papillomas or warts, that generally regress without devel­opment of any clinically recognized manifestations, but can occasionally persist and progress to malignancy. There are more than 100 HPV types, most of which infect the skin and cause warts on the hands or feet, and are rarely transmitted to the genital area. Over 40 types infect the human anogenital area of men and women, and are very common sexually transmitted agents, of which some can cause genital warts and others can lead to precursor cervi­cal lesions [CIN (cervical intraepithelial neoplasia)] and ICC [1,4].

In the past two decades, molecular epidemiological evidence has clearly indicated that certain HPV types are the central and necessary cause of cervical cancer [1]. Human papillomavirus DNA has been identified in almost all (99.7%) cases of cervical cancer worldwide [5], the most commonly found in ICC being HPV 16 (54%) and 18 (17%) [6]. According to the International Agency for Research on Cancer (IARC), at least 15 HPV types are significantly associated with progression of CIN to ICC and are considered carcinogenic and designated high-risk (HR) [6]. The odds ratio (OR) for cervical cancer associ­ated with the presence of any HPV is almost 160, which is higher than the association between smoking and lung cancer [6]. HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82 were classified as HR, HPV 26, 53 and 66 as probable HR, while HPV 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81 and CP6108 as low-risk (LR) (Table 2) [4]. Good agreement between the epidemiological classifi­cation and that based on phylogenetic grouping was found; most of these HR types are phylogenetically related to either HPV 16 (31, 33, 35, 52 and 58) or HPV 18 (39, 45, 59 and 68) [7]. In contrast to HR HPV types, LR types found in benign genital warts are only rarely detected in malignant lesions. In addition to cervical cancer, a major proportion of anal, perianal, vulvar, penile and oropharyn­geal cancers, appear also to be linked to the same HR HPV types [4].

In the USA, 75% of the 15- to 50-year-old female population is HPV-infected, 60% having transient infec­tion (as detected by antibodies), 10% having persistent infection (detected by DNA testing), 4% having cytologi­cal signs, and 1% having clinical lesions [8]. The preva­lence of HPV infection among sexually active women may range from 18 to 25%, depending on the age and the pop­ulation. Most HPV-infected individuals eliminate the virus within 6 to 24 months without ever developing any clinically recognized manifestations. It is important to emphasize that only very few (<1%) individuals with per­sistent HR HPV-infection will develop cervical cancer [1,6].

From 1996 to 1998, a study on the prevalence of HPV infection by means of polymerase chain reaction (PCR) was conducted among 1874 Croatian women (mean age 30.6; ranging from 15 to 78 years) having cytologycally evident cervical changes (LSIL and HSIL: low- and high-grade squamous intraepithelial) [9]. Two sets of general primers were used for HPV detection and specific primers for HPV 6/11, 16, 18, 31 and 33 were used for typing. A high level (64.4%) of cervical HPV infection was reported in the study group, of which 15 to 24-year-old women exhibited the highest level; 75% had HPV infection and were thus exposed to cervical carcinogenesis very early in life. The presence of HPV increased from 55 to 78% with the severity of the cervical lesions, from LSIL to HSIL, respectively. Most frequently observed was HPV 16, which was mostly associated with HSIL independent of patient age. These findings indicate that HPV infection, especially with HPV 16, represent a significant public health concern in Croatia.