Oncogenic human papillomaviruses (HPVs) are the major cause of cervical cancer and immortalize human keratinocytes (HKc) and cervical cells in culture [1-9]. The transforming activity of oncogenic HPVs resides primarily in the oncoproteins E6 and E7 [8]. The best characterized activities of these two proteins are their interactions with p53 and Rb, respectively, which result in disruption of cell cycle control, and produce genetic instability. It is universally accepted that oncogenic HPV infection is necessary to cause the initial changes that lead to cervical cancer. However, it is also clear that HPV alone is not sufficient to “drive” the process all the way to malignancy. Other host and environmental factors, many of which remain poorly defined, play pivotal roles in this process [1,9].  One of the key questions in the field, of particular significance under a clinical point of view, is: What exactly are those additional factors, and how do they work? This question is pivotal not only for the understanding of HPV-mediated transformation and the genesis of cervical cancer, but also for an understanding of factors that might determine racial disparities in the incidence, progression and outcome of this disease.

     Until anti-HPV vaccines become more cost effective, the best method for the detection and prevention of cervical cancer is to screen for the precursor lesions (by the Pap smear) and/or to screen for high-risk HPV infection. The combined use of Pap smear and HPV screening has the potential of identifying virtually all women at risk of developing invasive disease. This is true especially if screening includes typing the HPV, and distinguishing between transient and persistent infection [9]. However, the number of women that undergo colposcopy after repeatedly positive Pap smears (with or without added HPV testing) is far greater than the number of women who are truly at risk for invasive disease. In fact, most CIN I, II, and even CIN III lesions either persist or regress [1, 9-11]. Therefore, the identification of specific biomarkers of susceptibility to HPV-mediated transformation would help triage women who are most likely to regress, and would help identify women at the highest risk of progression who may need more aggressive treatment. Such biomarkers would contribute significantly to both the efficacy and the cost effectiveness of cervical cancer screening programs.

     Many of the co-factors that are postulated to determine progression of HPV-mediated lesions involve the type of immune response each individual patient develops in response to HPV infection. In particular, immunological factors are bound to affect whether a woman develops a transient or a persistent infection, and persistent HPV infection poses the highest risk for neoplastic lesions. Studies concerning these immunological factors have increased in recent years [for example see 12]. In addition to immunological factors, possible genetic determinants of susceptibility to HPV-mediated transformation and progression also need to be considered [13] and potential markers of susceptibility are currently being explored [14, 28].

     Although South Carolina’s cervical cancer mortality rates have decreased over the past several years (5.0 per 100,000 in 1989-1993 to 3.3 per 100,000 in 1993-1997), South Carolina’s age-adjusted mortality rates (1993-1997) have remained higher than the national average for all women (2.7/100,000) (South Carolina Cancer Registry 1999, 2000, Cancer Incidence Report).     

     In 1996, the South Carolina Central Cancer Registry was funded through CDC to begin enumerating incident cancer cases.  The data in 1997 indicate a 50% higher cervical cancer incidence rate among African-American women than Caucasian women, and a rate of cervical cancer mortality about 2.6 times higher among African-American women than Caucasian women in South Carolina (1993-1997).  Similar findings have been obtained in Georgia. Relative to other states, South Carolina’s mortality rate ranking, over the same time period, has fallen from being the state with the 4^th highest mortality rate to 8^th highest rate. Despite this modest improvement, cervical cancer remains a very important problem for South Carolina women. Such disparities in other populations have been attributed to different access to screening and follow-up for cervical cancer by different ethnic/racial groups, and this explanation is bound to bear some weight on the issue in South Carolina as well. However, our previous data on this issue indicate that access to care may not entirely explain this disparity and the possibility that host-cell, genetic and environmental factors may contribute to the disparity cannot at the present be ruled out.

Literature Cited