Cervical dysplasia: early intervention - Cervical Dysplasia

Alternative Medicine Review, May, 2003 by Keri Marshall

Abstract

Cervical cancer is the second-most common cancer in young women and is one of the most common causes of cancer deaths among women, particularly in minorities and in impoverished countries. Cervical dysplasia, a premalignant lesion that can progress to cervical cancer, is caused primarily by a sexually transmitted infection with an oncogenic strain of the human papillomavirus (HPV). Not all women with the virus develop cervical dysplasia or cervical cancer. It has been postulated there are multiple host factors that contribute to progression of disease. Many of these factors, such as nutrient deficiencies, can be reversed, which will result in regression of dysplastic lesions. Studies have shown dietary intervention and nutrient supplementation to be effective in preventing cervical cancer. Additionally, local escharotic treatment combined with systemic treatment shows significant potential in reducing dysplasia. Recent advances in vaccination technology demonstrate the effectiveness of an HPV vaccine. The vaccine, however, may have many social and cost-prohibiting limitations, as well as health side effects.

Introduction and Epidemiology

Cervical dysplasia is a premalignant lesion that can progress to cervical cancer, a common epithelial cancer that is the second-most common cancer in women age 20-39 years. (1) It disproportionately affects minority women and women living in underdeveloped countries. (2) Internationally, invasive cervical cancer accounts for 11.6 percent of all cancers. For every case of invasive cancer there are an estimated 50 cases of abnormal cervical smears that require monitoring and follow-up. (3) Current evidence suggests this lesion is primarily caused by a sexually transmitted infection with an oncogenic strain of the human papillomavirus (HPV). However, since this viral genome is found in healthy women as well as in healthy tissue adjacent to neoplastic lesions, factors unique to individual hosts appear to contribute to disease progression and dysplastic transformation.

Invasive cervical cancer develops from precursor lesions of the cervix called cervical intraepithelial neoplasia (CIN). Progression from normal tissue to invasive cervical cancer occurs through a series of increasing grades of cervical dysplasia (Figure 1). CIN I represents mild dysplasia and has a high rate of spontaneous remission (60%) and a low rate of progression to carcinoma. In contrast, approximately 38 percent of CIN II and III, moderate to severe dysplasia, will spontaneously regress, and 16-36 percent will progress to invasive cervical cancer. (4) Because reporting for CIN is not mandatory, the exact incidence is unknown. However, it is estimated that 2.5 million women are diagnosed with low-grade cervical abnormalities annually. (5)

[FIGURE 1 OMITTED]

Routine PAP smear screening is widely credited with reducing cervical carcinoma from the first to the eighth leading cause of cancer death in the United States, but the number of deaths attributable to the disease is still high (approximately 4,900 deaths). Additionally, the medical costs of providing PAP screening are considerable and a significant economic burden to health care systems. (6) Millions of ablative procedures (e.g. cryotherapy, electrocautery, cone biopsy) are performed each year as an approach to treatment. Screening is not available to all women, mainly due to lack of insurance or lack of insurance-wellness plans. In countries without screening, cervical cancer is the leading cause of cancer death in women.

Risk Factors

It is undisputed that infection with sexually acquired HPV is the primary risk factor for cervical cancer and plays a critical role in cervical carcinogenesis. (7,8) Several other cofactors have been implicated in the progression of low-grade to high-grade lesions and/or the development of cervical cancer, but these remain controversial in clinical trials. (9) These include early age at first intercourse, history of multiple sexual partners, oral contraceptive use, (10) high parity, low socioeconomic status, poor diet, cigarette smoking, (11) immunosuppression, (12) and promiscuous male sexual partners. (13) In one study, with respect to current use, the risk for cervical dysplasia increased for women who had been using oral contraceptives longer than 10 years. (14) A summary of risk factors is outlined in Table 1.

The correlation between cervical dysplasia and oral contraceptives is based on the premise that steroid hormones, such as estrogen and progesterone, are thought to play a role in the progression of disease. Progesterone has been reported to increase HPV-16 and HPV-18 gene expression at the levels of transcription and mRNA stability. (15,16) Most cases of cervical cancer are in the most estrogen-sensitive region of the cervix known as the transformation zone, (17) an area that displays a high level of conversion of estradiol to 16[alpha]-hydroxyestrone. When HPV-16 DNA immortalizes these cells, this activity increases eightfold. (18) Furthermore, the incidence of HPV DNA in exfoliated cervical cancer cells increases during pregnancy when estrogen levels are highest. (19)