Of the predominant gynecologic cancers, cancer of the uterine cervix is the least common, with only 11,270 new cases anticipated in the United States in 2009. Nevertheless, approximately 4,070 women die of cancer of the uterine cervix annually in the United States.
Epidemiology
Age The peak age of developing cervical cancer is 47 years. Approximately 47% of women with invasive cervical cancer are < 35 years old at diagnosis. Older women (> 65 years) account for another 10% of patients with cervical cancer. Although these older patients represent only 10% of all cases, they are more likely to die of the disease due to their more advanced stage at diagnosis.
Socioeconomic class Carcinoma of the uterine cervix primarily affects women from the lower socioeconomic class and those with poor access to routine medical care.
Geography Although invasive cervical carcinoma is relatively uncommon in the United States compared with the more common cancers in women (breast, endometrial, and ovarian cancers), it remains a significant health problem for women worldwide. In many developing countries, not only is cervical carcinoma the most frequently occurring cancer among middle-aged women, but also it is a leading cause of death. This is due, in part, to poor access to medical care and the unavailability of routine screening in many of these countries.
Etiology and risk factors
Sexual activity Invasive cervical carcinoma can be viewed practically as a sexually transmitted disease.
Human papillomavirus Molecular and epidemiologic evidence clearly indicates that certain types of human papillomavirus (HPV), which is sexually transmitted, are the principal causes of invasive cervical cancer and cervical intraepithelial neoplasia (CIN). More than 100 HPV types have been identified, and about 40 infect the genital tract. HPV-16 and HPV-18 are the types most commonly linked with cancer, present in 70% of cervical cancers and high-grade CINs. Two vaccines to prevent cervical cancer were approved by the FDA and became available in 2006 and 2009, respectively.
Age of onset of sexual activity Population studies of women with invasive cervical carcinoma have demonstrated that early age of onset of sexual activity also plays a role in the later development of the cancer. It is postulated that during the time of menarche in early reproductive life, the transformation zone of the cervix is more susceptible to oncogenic agents, such as HPV. Women who began sexual activity before 16 years of age or who are sexually active within 1 year of beginning menses are at particularly high risk of developing invasive cervical carcinoma.
Other risk factors include multiple sexual partners, a history of genital warts, and multiparity.
Cigarette smoking has been identified as a significant risk factor for cervical carcinoma. It is thought to increase risk by two-fold to five-fold. The mechanism may be related to diminished immune function secondary to a systemic effect of cigarette smoke and its by-products or a local effect of tobacco-specific carcinogens.
Oral contraceptives may also play a role in the development of invasive cervical carcinoma, although this theory is controversial. Given that most women who use oral contraceptives are more sexually active than women who do not, this may represent a confounding factor rather than a true independent risk factor. The exception may be adenocarcinoma of the cervix; this relatively uncommon histologic subtype may be related to previous oral contraceptive use.
Immune system alterations In recent years, alterations in the immune system have been associated with an increased risk of invasive cervical carcinoma, as exemplified by the fact that patients who are infected with the human immunodeficiency virus (HIV) have increased rates of both preinvasive and invasive cervical carcinomas. These patients also are at risk for other types of carcinoma, including Kaposi’s sarcoma, lymphomas, and other squamous cell carcinomas of the head and neck and the anogenital region. (For further discussion of AIDS-related malignancies, see chapter 24).
Data suggest that patients who are immunocompromised due to immunosuppressive medications also are at risk for both preinvasive and invasive cervical carcinomas. This association is probably due to the suppression of the normal immune response to HPV, which makes patients more susceptible to malignant transformation. An exciting recent development in the prevention of carcinoma of the cervix is the increasing use of HPV vaccines; if used on a timely basis in young women (ideally before they are exposed to the HPV virus), they can decrease this infection and eventually the incidence of cervical cancer.
Signs and symptoms
A symptom of advanced cervical carcinoma is intermenstrual bleeding in a premenopausal patient. Other commonly reported symptoms include heavier menstrual flow, menorrhagia, and/or postcoital bleeding. With effective screening, cervical cancer is generally asymptomatic.
Less frequently, patients with advanced cancer will present with signs of advanced disease, such as bowel obstruction and renal failure due to urinary tract obstruction. Only rarely are asymptomatic patients with a normal screening Pap smear found to have a lesion on the cervix as their only sign or symptom of cervical cancer. Foul-smelling vaginal discharge, pelvic pain, or both are occasionally observed.
Screening and diagnosis
Screening
Pap smear The paradigm for a cost-effective, easy-to-use, reliable screening test is the cervical cytology screen, or Pap smear. The introduction of the Pap smear has resulted in a significant reduction in the incidence of invasive cervical carcinoma, as well as a shift toward earlier stages at the time of diagnosis. The success of cervical cytology, as measured by the lowered incidence of cervical cancer, ironically has led to some controversy regarding the most effective application of this screening tool. With the marked reduction in the incidence of cervical carcinoma, more patients are screened and greater costs incurred to detect each additional case of cervical carcinoma.
Current screening recommendations The current recommendation of the American College of Obstetricians and Gynecologists (ACOG) is that all women who are 18 years of age or older and are sexually active be screened. If the patient has three consecutive annual cervical cytology smears that are normal, she may be safely screened at a less frequent interval of perhaps 2 to 3 years. There are no data to support screening patients on a less frequent basis. Any patient who has a history of cervical dysplasia should be screened at least on a yearly basis.
The current American Cancer Society (ACS) revised guidelines for cervical cancer screening follow: Cervical cancer screening should begin ~3 years after the onset of vaginal intercourse but no later than age 21. Cervical screening should be performed every year with conventional cervical cytology smears, or every 2 years using liquid-based cytology until age 30. After age 30, as an alternative to annual routine cytology, HPV DNA testing may be added to cervical cytology for screening. After this initial dual testing, women whose results are negative by both HPV DNA testing and cytology should not be rescreened before 3 years. Women whose results are negative by cytology but who are high-risk HPV DNA positive (type 16, 18, most commonly) are at a relatively low risk of having high-grade cervical neoplasia, and colposcopy should not be performed routinely in this setting. Instead, HPV DNA testing along with cervical cytology should be repeated in these women at 6 or 12 months. If test results of either modality are positive, colposcopy should then be performed. A randomized study of more than 10,000 women confirmed the evolving role of HPV testing as an accurate screening tool. In this study, women were randomized to undergo either conventional Pap testing or HPV testing as a screening method to identify high-grade CIN. The sensitivity and specificity for CIN 2/3 was 94.6% and 94.1% with HPV testing vs 55.4% and 96.8% for Pap tests. The sensitivity reached 100% when the tests were combined together.
