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It is now well established that the primary cause of cervical cancer is human papillomavirus. There are approximately 200 different types of HPV, 40–50 of which specifically infect the anogenital area. These types are mainly spread by skin contact during sexual activity.
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Of the genital HPV types, 15 are classified as ‘high risk’, as they are associated with anogenital cancer (including squamous and adenocarcinoma of the cervix). HPV 16 and 18 are responsible for around 70% of invasive cervical cancers and 50% of high-grade lesions.
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Prior to immunisation, infection with HPV was common and mostly transient, with 80% of women being infected with at least one genital type of HPV in their lifetime without ever knowing it. Cervical cancer is a rare outcome of HPV infection. Most cervical HPV infections are cleared or suppressed by cell-mediated immunity within 1–2 years of exposure. Persistent infection of the cervix with a high-risk HPV is known to cause high-grade cervical changes that, if left untreated, can progress to cervical cancer. More than 99.7% of cervical cancers test positive for HPV DNA.8
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The focus of attention is the transformation zone (see FIG. 98.1), where columnar cells lining the endocervical canal undergo metaplasia to squamous cells in the region of the squamocolumnar junction. It is important clinically to realise that this transformation zone can extend with progressive metaplasia of columnar epithelium and so the squamocolumnar junction may recede into the endocervical canal. This is a feature in postmenopausal women (see FIG. 98.2). As squamous cell carcinoma almost always arises in the transformation zone, it is vital that cells from this area are sampled.
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HPV and the natural history of cervical neoplasia9
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Low-grade squamous intraepithelial lesions (LSILs) represent an acute HPV infection of the transformation zone. LSILs are seen with both low- and high-risk HPV types. Most women will clear the virus over about 10 months with no lasting effect. Persistent infection with an oncogenic HPV type causes precancerous changes (high-grade squamous–intraepithelial lesion or HSIL).
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HSILs may return to normal, persist or eventually progress to invasive cervical cancer. The average duration between HSILs and cancer is between 10 and 15 years. However, women with histologically confirmed moderate to severe dysplasia require a colposcopic assessment. FIGURE 98.3 and TABLE 98.1 illustrate the disease spectrum of cervical neoplasia.
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Clinical presentation
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Many patients with cervical cancer are asymptomatic and when early symptoms do arise they are often dismissed as of little consequence.
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Symptoms, if present, may be:
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irregular vaginal bleeding, especially postcoital or intermenstrual bleeding
postmenopausal bleeding
vaginal discharge
symptoms of advanced disease (e.g. back pain, fatigue, vaginal fistula)