Neoplastic Conditions

The two main malignant neoplasms to occur within the cervix are invasive squamous cell carcinoma and adenocarcinoma. Mainly due to the advent of organised screening programmes, precursor lesions (CIN and CGIN) are identified much more commonly by cytology and the incidence of invasive cervical tumours is decreasing.

Cervical Intraepithelial Neoplasia (CIN): CIN is the preferred designation in the UK for the spectrum of dysplastic preinvasive squamous lesions which are associated with an increased risk of the subsequent development of cervical squamous carcinoma. These usually arise at the transformation zone of the cervix and are divided into CINI, CINII and CINIII (previously known as mild, moderate and severe dysplasia respectively). Morphological changes associated with HPV infection are termed koilocytosis. In some countries koilocytosis and CINI are collectively termed low-grade squamous intraepithelial lesion (LSIL) while CINII and CINIII are designated highgrade squamous intraepithelial lesion (HSIL). The transition from CINI to CINIII may take many years and all grades of CIN may revert to normal, especially CINI. The aim of cervical screening is to pick these lesions up in the preinvasive stage. Treatment then reduces the risk of development of squamous carcinoma.

Cervical Glandular Intraepithelial Neoplasia (CGIN): similar to the situation with CIN, preinvasive glandular lesions may be encountered. These are much rarer than the corresponding squamous lesions and are less likely to be picked up on cytological examination. They often coexist with squamous lesions. In the UK the preferred designation is cervical glandular intraep-ithelial neoplasia (CGIN). These are divided into low-grade and high-grade CGIN. The WHO classification uses the terms glandular dysplasia (atypical hyperplasia) and adenocarcinoma in-situ, corresponding to low-grade and high-grade CGIN respectively. Many of these lesions are associated with HPV infection.

Invasive tumours: approximately 70-80% of invasive carcinomas of the cervix are squamous cell in type. Most of the remainder are adenocarcinomas. Rarer morphological subtypes include adenosquamous carcinoma and neuroendocrine small cell carcinoma. A variety of other malignant tumours occur within the cervix but these are rare.

The main risk factor in the development of both squamous carcinoma and adenocarcinoma of the cervix is infection with HPV. There may be an association with oral contraceptive use and cervical adenocarcinoma. Other factors implicated in the pathogenesis of cervical cancer, including early age at first intercourse, multiple sexual patterns, etc., are not independent of HPV infection. Smoking is also a risk factor for the development of cervical squamous carcinoma.

Treatment: following referral because of an abnormal cervical smear (or occasionally a clinically suspicious cervix or symptoms such as postcoital bleeding) colposcopic examination is performed. In general, low-grade lesions (koilocytosis and CINI) are treated by local ablative procedures or cytological follow-up while high-grade lesions (CIN II and CIN III) are treated by local excision. Usually this is in the form of diathermy large-loop excision of the transformation zone (LLETZ) of the cervix. Occasionally, cold-knife cone biopsies may be performed, especially if a small invasive carcinoma is suspected or if a cervical glandular lesion is suggested on cytology. With more advanced cervical tumours (usually greater than stage Ia) radical hysterectomy is usually carried out. This involves removing the uterus and cervix with a cuff of vagina. The surrounding parametrium on both sides is also removed and pelvic lymph nodes are sampled. The FIGO staging system for cervical cancer is used. With advanced cervical cancers the initial treatment may be radiotherapy or chemoradiation. This may be followed by salvage hysterectomy at a later date. Whether radiation or chemoradiation is given post surgery for cervical carcinomas depends on careful clinical and pathological staging.

Cone biopsies with careful assessment of margins and cytological follow-up may be performed in patients with early (stage Ia) tumours. Occasionally, in young patients with early stage Ib cancers (usually less than 2 cm) and who wish to preserve their fertility, a trachelectomy may be performed followed by the insertion of a suture into the cervix. Trachelectomy involves a local excision of the cervix with the surrounding parametrium. Pelvic lymph nodes are usually sampled laparoscopically during this procedure. Careful pathological examination is required to ascertain whether further, more radical, surgery is needed. All cases should be discussed at a multidisci-plinary gynaecological oncology meeting.

Prognosis: following ablative or local excision of pre-malignant cervical lesions, close cytolog-ical follow up is carried out for a period of 5-10 years depending on the diagnosis.

The prognosis of invasive cervical cancers is largely dependent on the tumour stage. Microinvasive carcinomas (variously defined as stage Ia1 or Ia2 carcinomas) have an excellent prognosis and these may be treated by conservative local excision therapies, usually in the form of loop or cone biopsies. The prognosis of more advanced cervical cancers, as already stated, largely depends on the stage of the tumour, especially the presence of extracervical spread, with an overall five-year survival of about 55%.

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