Cervical carcinoma

Squamous cell carcinoma is the most common histologic subtype of cervical cancer, accounting for approximately 80% of cases. As outlined above, HSIL is an immediate precursor of cervical squamous cell carcinoma. The second most common tumor type is cervical adenocarcinoma, which constitutes about 15% of cervical cancer cases and develops from a precursor lesion called adenocarcinoma in situ. Adenosquamous and neuroendocrine carcinomas are rare cervical tumors that account for the remaining 5% of cases. All of the above tumor types are caused by high oncogenic risk HPVs. The clinical characteristics and risk factors are the same for each tumor type, with the exception that adenocarcinomas and adenosquamous and neuroendocrine carcinomas typically present with advanced-stage disease. This unfortunate outcome occurs because Pap screening is less effective in detecting these cancers. Patients with adenosquamous and neuroendocrine carcinomas, therefore, have a less favorable prognosis than patients with squamous cell carcinomas or adenocarcinomas. The peak incidence of invasive cervical carcinoma is 45 years. With the advent of widespread screening, many cervical carcinomas are detected at a subclinical stage, during evaluation of an abnormal Pap smear.

Morphology. Invasive cervical carcinoma may manifest as either fungating (exophytic) or infiltrative cancers.

On histologic examination, squamous cell carcinomas are composed of nests and tongues of malignant squamous epithelium, either keratinizing or nonkeratinizing, invading the underlying cervical stroma (Fig. 22-19). Adenocarcinomas are characterized by proliferation of glandular epithelium composed of malignant endocervical cells with large, hyperchromatic nuclei and relatively mucin-depleted cytoplasm, resulting in dark appearance of the glands, as compared with the normal endocervical epithelium (Fig. 22-20A). Adenosquamous carcinomas are tumors composed of intermixed malignant glandular and malignant squamous epithelium. Neuroendocrine cervical carcinomas typically have an appearance similar to small-cell carcinoma of the lung (see Chapter 15); however, in contrast to the lung tumor, which is not related to HPV infection, cervical small-cell carcinomas are positive for high oncogenic risk HPVs.

Advanced cervical carcinoma extends by direct spread to involve contiguous tissues, including the paracervical tissues, urinary bladder, ureters, rectum, and vagina. Local and distant lymph nodes are also involved. Distant metastases may be found in the liver, lungs, bone marrow, and other structures.

Stage 0.

Carcinoma in situ (CIN III, HSIL)

Stage I.

Carcinoma confined to the cervix

Ia.

Preclinical carcinoma, that is, diagnosed only by microscopy

Ia1.

Stromal invasion no deeper than 3 mm and no wider than 7 mm (so-called microinvasive carcinoma) (see Fig. 22-19A)

Ia2.

Maximum depth of invasion of stroma deeper than 3 mm and no deeper than 5 mm taken from base of epithelium; horizontal invasion not more than 7 mm

Ib.

Histologically invasive carcinoma confined to the cervix and greater than stage Ia2

Stage II.

Carcinoma extends beyond the cervix but not to the pelvic wall. Carcinoma involves the vagina but not the lower third.

Stage III.

Carcinoma has extended to the pelvic wall. On rectal examination there is no cancer-free space between the tumor and the pelvic wall. The tumor involves the lower third of the vagina.

The false-negative error rate of the Pap test is around 10% to 20%. Most of these false-negative tests stem from sampling errors. Recommendations for the frequency of Pap screening vary, but in general the first smear should be at age 21 years or within 3 years of onset of sexual activity, and thereafter on an annual basis. After age 30, women who have had three consecutive normal cytology results may be screened every 2 to 3 years.27

As an adjunct to cytology, HPV DNA testing may be added to cervical cytology for screening in women aged 30 years or older. Women with normal cytology result and negative HPV DNA testing may be rescreened every 3 years. Women with a normal cytology result, but who are high-risk HPV DNA-positive, should have cervical cytology repeated at 6 to 12 months.28 HPV testing of women younger than 30 is not recommended because of the high prevalence of HPV infection in this age group and the low specificity of the positive result (see Fig. 22-15).

When the Pap test is abnormal, a colposcopic examination of the cervix and vagina is performed to delineate the extent of the lesion and to target the areas to be biopsied. Application of acetic acid to the cervix highlights abnormal areas. After confirmation by tissue biopsy, women with LSIL can be followed in a conservative fashion with repeat smears and close follow-up. Some gynecologists use local ablative measures based upon their experience with the disease and reliability of patient follow-up. HSILs are treated with cervical conization (excision).29 Follow-up smears and clinical examinations should continue for life, since vaginal, vulvar, or cervical precancers and cancers may later develop.

In 2006 the FDA licensed a quadrivalent, prophylactic HPV vaccine for HPV types 6, 11, 16, and 18. This vaccine is designed to reduce the incidence of cervical cancer caused by HPV 16 and HPV 18 (together accounting for approximately 70% of cervical cancer cases22) and vulvar condylomas (HPV 6 and 11). In phase III trials the vaccine prevented 100% of HPV 16/18-associated HSILs. The vaccine is prepared from noninfectious, DNA-free virus-like particles produced by recombinant technology. It induces high levels of serum antibodies in all vaccinated individuals. In women who have no evidence of past or current infection with the HPV genotypes included in the vaccine, there is protection from HPV infection for up to 5 years after vaccination; longer follow-up studies are still pending. Since the HPV vaccine does not eliminate the risk of cervical cancer due to other oncogenic HPV types, cervical cancer screening should still continue according to past guidelines to minimize cancer incidence.

Дата добавления: 2015-11-13