Chapter 98

### Introduction

‘What we’ve done is found a way of preventing one particular cancer. It’s not absolute, in the sense that you’d have to get there not only before the cancer, but before the infection that causes the cancer.’

Professor Ian Frazer, Enough Rope, 2006

##### Cervical cancer

Cervical cancer is the fourth most common cause of cancer death in women worldwide, especially in developing countries.1 It is the most common cancer in women in Eastern and Middle Africa, and the 12th most common in Australian women.1,2 Australia has the second lowest incidence of cervical cancer in the world as a result of the success of the National Cervical Screening Program introduced in 1991, which has halved its incidence.2

The most common cervical cancer is squamous cell carcinoma (SCC), accounting for 80% of cases. Adenocarcinoma is less common and more difficult to diagnose because it starts higher in the cervix. Cervical cancer almost exclusively occurs in women who have been sexually active, due to exposure to human papillomavirus (HPV). Other risk factors include smoking, multiparity, immunosuppression and exposure to diethylstilboestrol in utero.3

### Cervical cancer and human papillomavirus4

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 spread through genital skin-to-skin contact. 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. Infection with HPV is common and mostly transient, with 80% of women being infected with at least one genital type of HPV in their lifetime. 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.5

#### Basic pathology

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 are taken from it when performing a Pap test.

###### FIGURE 98.1

The ...

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