Cervical Dysplasia and Cancer

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Chapter 38 Cervical Dysplasia and Cancer

Cervical cancer kills about 250,000 women a year worldwide and is the most common cause of death from cancer in women. About 80% of new cases reported each year occur in developing countries. In developed countries, regular screening with Papanicolaou (Pap) smears has markedly decreased the incidence of the disease, and most cases now occur in women who have not had regular Pap smears. In the United States, cervical cancer now ranks only 13th among cancers in women, with 11,150 new cases expected in 2007, and 3,670 deaths.

Studies have identified persistent infection with a high-risk human papillomavirus (HPV) as the cause of virtually all cervical cancers. Recent randomized clinical trials of prophylactic HPV vaccines have demonstrated dramatic efficiency in preventing HPV 16 and 18 infections as well as precancerous cervical lesions. Although it will take several decades to demonstrate a decreased incidence of invasive cervical cancer, with widespread use, HPV vaccination has the potential to markedly decrease the incidence of cervical cancer in future generations.

image Screening of Asymptomatic Women

The American College of Obstetricians and Gynecologists has recommended that all women undergo an annual physical examination, including a Pap smear, within 3 years of sexual intercourse, or by age 21 years. Annual screening should occur until age 30 years. If there have been three consecutive negative tests, screening may occur every 2 or 3 years at the discretion of the treating physician. Both the endocervical canal and the ectocervix should be sampled when taking the Pap smear.

The false-negative rate for conventional Pap smears for high-grade intraepithelial lesions is generally reported to be about 20%, but it is higher for glandular lesions and for invasive cancers.

New technologies have been developed to decrease the false-negative rate. ThinPrep (Cytyc, Marlborough, Mass) and SurePath (BD Diagnostics–TriPath, Franklin Lakes, NJ) are automated liquid-based slide-preparation systems. With liquid-based cytology, the spatula or brush taking the smear is placed into a fixative solution, instead of smearing the cells directly onto a glass slide. Blood, mucus, and inflammatory cells are eliminated, and a monolayer smear is then automatically prepared by a machine. BD Focal Point (BD Diagnostics–TriPath) and ThinPrep Imager (Cytyc) are computerized image processors that select the most abnormal cells on a slide. They increase the sensitivity of slide reading, while decreasing the time needed by the cytotechnician to read each slide, thereby improving the cost-effectiveness of screening.

The cost-effectiveness of HPV DNA testing as a primary screening test, either alone or in combination with cervical cytology, in women aged 30 years or older, is currently under investigation. HPV DNA testing is much more sensitive than cervical cytology, but less specific.

Women should have regular cervical screening even if they have received the HPV vaccine because the vaccine does not protect against all high-risk HPV viral types.

image Cervical Topography

During early embryonic development, the cervix and upper vagina are covered with columnar epithelium. During intrauterine development, the columnar epithelium of the vagina is progressively replaced by squamous epithelium. At birth, the vagina is usually covered with squamous epithelium, and the columnar epithelium is limited to the endocervix and the central portion of the ectocervix. In about 4% of normal female infants and about 30% of those exposed to diethylstilbestrol in utero, the columnar epithelium extends onto the vaginal fornices. Macroscopically, the columnar epithelium has a red appearance because it is only a single cell layer thick, allowing blood vessels in the underlying stroma to show through it.

The embryologic squamous and columnar epithelia are designated the original and native squamous and columnar epithelia, respectively. The junction between them on the ectocervix is called the original squamocolumnar junction.

Throughout life, but particularly during adolescence and a woman’s first pregnancy, metaplastic squamous epithelium covers the columnar epithelium so that a new squamocolumnar junction is formed more proximally. This junction moves progressively closer to the external os and then up the endocervical canal. The transformation zone is the area of metaplastic squamous epithelium located between the original squamocolumnar junction and the new squamocolumnar junction (Figure 38-1).

image Classification of an Abnormal Papanicolaou Smear

In 1988, a consensus meeting was convened by the Division of Cancer Control of the National Cancer Institute to review existing terminology and to recommend effective methods of cytologic reporting. As a result of this meeting, the Bethesda system was devised and requires (1) a statement regarding the adequacy of the specimen for diagnosis, (2) a diagnostic categorization (normal or other), and (3) a descriptive diagnosis. A revised Bethesda system was developed in 2001 and is shown in Box 38-2.

BOX 38-2 Bethesda Classification of Cytologic Abnormalities (2001, Abridged)