2007;177(1488-2329 (Electronic), 5):444C5. BACKGROUND Description of the condition Association between human papillomavirus (HPV) contamination and cervical cancer and other HPV-related cancers and their precursors The development of cervical cancer passes through a number of phases: (a) contamination of the cervical epithelium with certain human papillomavirus (HPV) types; (b) persistence of the HPV contamination; (c) progression to precancerous lesions (cervical intraepithelial neoplasia (CIN) and (d) eventually invasion. All phases are reversible, except for the last one (Bosch 2002; Castellsague 2006; IARC 2007). Recently, an IARC (International Agency for Research on Cancer) expert group reviewed the carcinogenicity of human papilloviruses and confirmed that for 12 HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, Rabbit Polyclonal to hnRNP H 52, 56, 58, and 59) sufficient evidence exists that they are causally linked with the development of cervical cancer (Bouvard 2009). Type HPV 68 is considered as probably carcinogenic (Schiffman 2009). The HPV type 16, in particular, has a high potential for malignant transformation of infected cervical cells (Schiffman 2005). The HPV types 16 and 18 jointly cause 70% of all the cervical Chlortetracycline Hydrochloride cancers worldwide (Munoz 2004). Moreover, HPV type 16 is also linked with rarer types of cancer, namely malignancy of the vulva and vagina in women, penis malignancy in men and anus, oropharynx and larynx cancer in women and men (Cogliano 2005; IARC 2007). IARC 2007 The main route of HPV transmission is sexual. Contamination with HPV usually occurs soon after the onset of sexual activity (Winer 2003; Winer 2008). The prevalence of HPV contamination generally peaks in late teenage or early twenties and declines thereafter (De Chlortetracycline Hydrochloride Sanjose 2007). Human papillomavirus contamination usually clears spontaneously, in particular in women younger than 30 years. Human papillomavirus contamination can result in intraepithelial neoplastic cellular lesions which are identifiable by cytological examination (ASCUS, LSIL, HSIL, see list of abbreviations in Appendices) and which can be confirmed histologically (CIN1-3)*. These lesions generally regress, but the probability of regression decreases, and the likelihood of progression to cancer increases with the duration of HPV contamination and the severity of the lesion. From historical data, it has been estimated that CIN3 incurs a probability of progressing to invasive cancer of 12% to 30%; whereas for CIN2 this probability is substantially less (McCredie 2008; Ostor 1993).The natural history of HPV infection to invasive cancer takes a minimum of 10 years and a median of approximately 25 to 30 years (IARC 2007). A World Health Business (WHO) expert group accepted a reduction in the incidence of high-grade CIN (CIN2+) and cervical adenocarcinoma (AIS) or worse as an acceptable surrogate outcome of HPV vaccination trials, since the reduction of the incidence of invasive cervical cancer would require large and lengthy studies which are unlikely to be undertaken (Pagliusi 2004). The low-risk HPV types 6 and 11 cause approximately 90% of genital warts in women and men (Lacey 2006). They occur in low-grade dysplastic cervical lesions but are not associated with cervical cancer (IARC 2007). Moreover, HPV types 6 and 11 cause recurrent respiratory papillomatosis, a rare but very serious disease Chlortetracycline Hydrochloride of the upper airways often requiring repetitive surgical interventions (Lacey 2006). The recognition of the strong causal association between HPV contamination and cervical cancer has resulted in the development of HPV assays to detect cervical cancer precursors (Iftner 2003), and even vaccines that prevent HPV contamination (prophylactic vaccines) or that treat HPV-induced lesions (therapeutic vaccines) (Frazer 2004; Galloway 2003; Schneider 2003). Therapeutic vaccines are still in very early experimental phases and are not further considered in this review. * Throughout this review, we will use the 2001 Bethesda System to define cytologically defined neoplastic lesions of the cervical epithelium (Solomon 2002) and the CIN nomenclature to define histologically confirmed cervical intraepithelial neoplasia (Richart 1973). Burden Chlortetracycline Hydrochloride of cervical cancer Cervical cancer is the second most common cancer in women worldwide (Ferlay 2004). It is estimated that in 2002, approximately 493,000 women developed cervical cancer and that 273,000 died from the disease (Ferlay 2004). Eighty-three per cent of cervical cancer cases occur in developing countries. Chlortetracycline Hydrochloride Cervical cancer is the predominant female malignancy in Sub-Saharan Africa, Central America and South-Central Asia, where a womans risk of developing this disease by age 65 years ranges between 2.1% and 3.2%. In many developed countries, the incidence of, and mortality from, squamous cervical cancer has dropped substantially over the last decades as a consequence of widespread screening (Arbyn 2009; Arbyn 2009a; Bray 2005a; IARC 2004). For instance, In the USA and North and West-Europe, the cumulative risk of cervix uteri cancer up to age 65 years is usually 0.7% or lower (Ferlay 2004). However, approximately 52,000 and 13,000 cases.