The initiating event in cervical dysplasia and carcinogenesis is infection with HPV. HPV infection was detected in up to 99% of women with squamous cervical carcinoma. HPV is the causative agent in both squamous and adenocarcinoma of the cervix, but the respective tumors may have different carcinogenic pathways (7). There are more than 100 different types of HPV, more than 30 of which can affect the lower genital tract. There are 14 high-risk HPV subtypes; two of the high-risk subtypes, 16 and 18, are found in up to 62% of cervical carcinomas. The mechanism by which HPV affects cellular growth and differentiation is through the interaction of viral E6 and E7 proteins with tumor suppressor genes p53 and Rb, respectively. Inhibition of p53 prevents cell cycle arrest and cellular apoptosis, which normally occurs when damaged DNA is present, whereas inhibition of Rb disrupts transcription factor E2F, resulting in unregulated cellular proliferation (8). Both steps are essential for the malignant transformation of cervical epithelial cells. Two HPV vaccines, the quadrivalent Gardasil and the bivalent Cervarix, are approved by the U.S. Food and Drug Administration (FDA) and protect against subtypes 16 and 18. After 3 years, the efficacy of Gardasil was 99% for preventing cervical intraepithelial neoplasia grades 2 and 3 caused by HPV 16 or 18 in females who were not previously infected with either HPV 16 or 18 before vaccination; however, efficacy was only 44% in those who were infected prior to vaccination (9). Because the quadrivalent and bivalent HPV vaccines both protect only against certain types of HPV, vaccinated women need to continue to receive Pap test screening according to guidelines.
Evaluation Vaginal bleeding is the most common symptom occurring in patients with cancer of the cervix. Most often, this is postcoital bleeding, but it may occur as irregular or postmenopausal bleeding. Patients with advanced disease may present with a malodorous vaginal discharge, weight loss, or obstructive uropathy. In asymptomatic women, cervical cancer is most commonly identified through evaluation of abnormal cytologic screening tests. The false-negative rate for Pap tests in the presence of invasive cancer is up to 50%, so a negative Pap test should never be relied on in a symptomatic patient (10).
Initially, all women suspected of having cervical cancer should have a general physical examination performed to include evaluation of the supraclavicular, axillary, and inguinofemoral lymph
Figure 36.1 Gross appearance of cervical cancer on examination.
Colposcopic Findings of Invasion nodes to exclude the presence of metastatic disease. On pelvic examination, a speculum is inserted into the vagina, and the cervix is inspected for suspicious areas (Fig. 36.1). The vaginal fornices also should be closely inspected. With invasive cancer, the cervix is usually firm and expanded, and these features should be confirmed by digital examination. Rectal examination is important to help establish cervical consistency and size, particularly in patients with endocervical carcinomas. Rectal examination is the only way to determine cervical size if the vaginal fornices have been obliterated by menopausal changes or by the extension of disease. Parametrial extension of disease is best determined by the finding of nodularity beyond the cervix on rectal examination.
When obvious tumor growth is present, a cervical biopsy is usually sufficient for diagnosis. If gross disease is not present, a colposcopic examination with cervical biopsies and endocervical curettage is warranted. If the diagnosis cannot be established conclusively with colposcopy and directed biopsies, which may be the case with adenocarcinoma, cervical conization may be necessary.