CANCER - CERVICAL
Definition
Cervical dysplasia refers to neoplastic changes in the cervical epithelium. Previously called cervical intraepithelial neoplasia (CIN), it is now called squamous intraepithelial lesion (SIL) and classified as low grade (LSIL) or high grade (HSIL), according to the Bethesda system. The degree of neoplasia is determined based on the extent of mitosis, nuclear atypia, and cell immaturity. The morphological continuum toward cervical cancer ranges from low to high grade cellular changes involving the full thickness of the epithelium (CIN III, which is biologically equivalent to carcinoma in situ). LSIL has a very slow rate of progression and a high rate of spontaneous regression. When considered together, however, as many as 66% of all stages of SIL are estimated to progress to cancer within 10 years. Interestingly, a full 2% of women with Pap smear reports of benign cellular changes actually have HSIL at the time of the evaluation, illustrating the need for improvement in screening techniques and treatment of any premalignant lesions. While numerous contributing factors have been established, the exact aetiology of CIN (as it is still commonly called) is unknown. There is epidemiologic evidence of a correlation between precancerous and cancerous changes in the cervical epithelium and human papillomavirus (HPV); HPV DNA is found in 80% to 100% of squamous cancers of the cervix. However, HPV takes decades to progress to cancer, and only a small percentage of those with HPV ever develop an invasive cancer. In addition, studies on mice suggest that HPV alone is not sufficient for carcinogenesis. It is likely that other factors known to correlate with dysplasia may work synergistically with HPV to initiate carcinogenic changes through a still unknown mechanism.
Aetiology / Risk Factors
- HPV infection (types 16, 18, 31, 33, and 50s tend to be high grade; types 6 and 11 tend to be low grade)
- Smoking
- Early age of first intercourse
- Multiple sexual partners or a partner with many sexual partners
- High risk males as sexual partners (e.g., males whose former partner had cervical cancer)
- History of other sexually transmitted diseases
- Human immunodeficiency virus (HIV) (seropositivity correlates to 40% incidence of cervical dysplasia; possibly as a result of persistent HPV infections in that population)
- Other causes of immunosuppression
- Long-term oral contraceptive (OCP) use (35 years, relative risk of 1.5)
- Diethylstilbestrol (DES)-exposed in utero
- Genital warts (condylomata)—HPV types 6, 11, and 35
- Low RBC folate levels (often present with OCP use: even when serum levels of RBCs are normal with OCP use, diminished cellular uptake of folate may occur) may enhance infectivity with HPV; some report that cytologic changes related to reduced levels of folate may precede deficient measurements in serum.
- Vitamin A, beta-carotene, selenium, vitamin E, and vitamin C dietary deficiencies, some epidemiologic evidence; data is somewhat mixed
- Herpes simplex virus—weak evidence
Symptoms & Signs
- Frequently asymptomatic
- Genital condylomata acuminatum at any site—occasional
- Cervical cancer—abnormal bleeding or postcoital spotting; yellow vaginal discharge, low back pain, and urinary symptoms also possible