Cervical neoplasia

Published on 09/03/2015 by admin

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Chapter 19 Cervical neoplasia

Amy Tang

Role of human papillomavirus

Over 60 different genotypes of human papillomavirus (HPV) have been identified. In some populations, it is present in over 70% of women and may be a vaginal commensal. Other co-factors, such as smoking, may be required to promote the development to cervical intraepithelial neoplasia (CIN).

Link with cervical cancer

• HPV has been identified in benign conditions and cancer.
• Infection with HPV is present in over 90% of preinvasive or invasive cervical neoplasia.
• High-risk HPV subtypes include types 16, 18, 31, 33 and 35.

Management

• Up to 10% of women will have HPV on cervical cytology at some stage.
• If HPV only on cytology, 35%–40% will have CIN on further investigations.
• There is no risk of cancer in patients with HPV without CIN.
• If only HPV is present and this is not treated, 20%–25% progress to CIN in 2 years, which persists in 30%–40% of these patients.
• If treated, the rate of progression is similar to untreated.
• There is no evidence that examining or treating male partners changes the outcome for women.
• There is no evidence that wearing condoms reduces the progression of HPV to CIN.

Cervical cytology

When to perform cervical cytology

The best time is at mid-cycle. In the absence of abnormal bleeding and previous abnormal cervical cytology or treatment, smears should be taken every 2 years. When sexually active, perform the first smear test within 2 years of the first sexual intercourse or from 18–20 years of age, whichever is later. Cease at age 70 years if there have been two normal smears within the past 5 years. In women who have had a hysterectomy and who previously had normal cytology, no further smears are required.

Screening for CIN

Cervical cytology

• is 99.7% specific (i.e. has a false-positive rate of 0.3%)
• is 80% sensitive (with a false-negative rate of 20%)

Computer-assisted screening

• Liquid-based cytology (ThinPrep) with automated image analysis technology can reduce the number of unsatisfactory smears and improve the sensitivity to detect cervical dysplasia.

Possible reasons for false-negatives

• sampling error
• incorrect fixative (95% ethyl alcohol fixative is required)
• timing of smear (best at mid-cycle)
• amount of sample (too little/too much)
• screening error
• interpretive error

Endocervical cells present

• means that the squamocolumnar junction is reached (i.e. the upper limit of the transformation zone)
• <1% of smears containing no endocervical cells (and no abnormal cells seen) is an abnormal result

Effectiveness against cervical cancer

• If a smear is performed every year and appropriate management is undertaken, cervical cancer is reduced by 93.5%.
• If performed every 2 years, cancer may be reduced by 92.5%.
• If performed every 3 years, cancer may be reduced by 90.8%.

HPV testing

• Preliminary data suggest that HPV testing is a feasible technique for primary screening for cervical cancer. However, it has not been shown to be a cost-effective screening tool in the Australian context.
• It may be useful in the triage of equivocal cytology results or low-grade lesions.
• In Australia, it is used as a ‘test of cure’ for high-grade cervical dysplasias. Pap smear and HPV typing is carried out at 12 months after treatment and annually thereafter, until both tests are negative on two consecutive occasions. Patients can then have smears every 2 years.

Terminology for cervical cytology/Pap smear reporting

The Bethesda System 2001 for squamous abnormalities

• atypical squamous cells of undetermined significance (ASCUS)
• low-grade squamous intraepithelial lesion (LSIL): includes HPV and CIN1
• atypical squamous cells, possible high-grade lesion (ASC-H)
• high-grade squamous intraepithelial lesion (HSIL): includes CIN2 and CIN3
• squamous cell carcinoma

The Australian Modified Bethesda System 2004

• possible low-grade squamous intraepithelial lesion
• low-grade squamous intraepithelial lesion (HPV and CIN1)
• possible high-grade squamous intraepithelial lesion
• high-grade squamous intraepithelial lesion (CIN2 and CIN3)
• squamous cell carcinoma

Management of abnormal Pap smear

• If LSIL, repeat Pap smear in 12 months; then 24 months if normal result. Otherwise refer for colposcopy
• If possible HSIL or HSIL, refer for colposcopy and biopsy.

Cervical intraepithelial neoplasia (CIN)

Definition. Normally, as cells differentiate and mature they move towards the surface. Abnormalities result in mitotic figures, nuclear pleomorphism, and changes in the nuclear-to-cytoplasmic ratio.

• CIN1: two-thirds or more of the upper epithelium showing good differentiation
• CIN2: maturation/differentiation in the upper half of the epithelium with mitotic figures in the basal half
• CIN3: less than one-third of the upper epithelium showing differentiation

Progression of CIN

• Incidence varies in different studies.
• CIN1 progressing to higher CIN lesions: about 16%–25% in 2–4 years.
• CIN3 to invasive cancer: about 18%–35% in 1–23 years.

Management

Colposcopy

• Aims: identify abnormal area and exclude invasive disease.
• The transformation zone needs to be seen. This is the area between the original and existing squamocolumnar junction. The columnar epithelium undergoes metaplasia as the transformation zone extends. The squamocolumnar junction may recede up the endocervical canal (e.g. in postmenopausal women). The pathological process often occurs in the transformation zone.
• With 3%–5% acetic acid, abnormal epithelium turns acetowhite.
• Schiller’s test: columnar or abnormal squamous epithelium has little or no glycogen and does not stain with iodine.
• Colposcopic changes seen with CIN lesions are punctation (vessels are perpendicular to surface), mosaic (capillaries parallel to surface), and atypical vessels irregular in size, shape and course.

Conservative treatment

Current Australian guidelines recommend that histologically proven low-grade squamous abnormalities can be safely managed by repeat Pap smears at 12 and 24 months. If persistent possible or definite LSIL, annual smears should be continued until at least two are negative.

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