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There have been many studies to determine the cause or causes of cervical cancer during the last 50 years. Most of the studies have involved comparison of women with CIN or invasive cancer with women with normal cervices. The women are matched for age, parity, and social status in order to identify the causative agent(s) or co factors responsible for the development of cervical neoplasia. Despite extensive studies, no single factor emerges as the sole cause of the disease and it is probable that a number of factors are operating in combination. These include sexual behaviour, contraceptive use, smoking and immunological status . There is also strong evidence that a sexually transmitted agent is involved and the human papilloma viruses are the prime suspects at this time.
- Human papilloma virus: DNA analysis of anogenital warts,CIN and cervical cancerous tissue has shown that two groups of HPV can be identified in the female genital tract. One group of HPV (type 6,11)is almost always associated with low grade CIN lesions and exophytic anogenital warts which have a low risk of progressing to cervical cancer. A second group (HPV type 16, 18) is found most commonly in CIN2 and CIN3 which have a high risk of developing into invasive cancer.
- Sexual activity: The association between sexual activity and cervical cancer has been known for over a century. In 1892 Rigoni Stern examined the death records in Verona and recorded that uterine cancer was common in married women but rare in unmarried women or nuns. More recent studies showed that the age of first coitus (Rotkin 1967) and number of sexual partners (Harris et al1980) are important risk factors for CIN and cervical cancer. Contrary to earlier beliefs, circumcision does not reduce the cancer risk.
- Contraceptive use: There have been many studies to investigate the risks of cervical cancer in women who take oral contraceptives. These studies are complex because of the many different oral contraceptives available and use is intermittent. A recent study carried out by the International Agency for Research on Cancer (2002) found that prolonged use of the oral contraceptive pill increased the risk of cervical cancer only in women infected with one of the high risk human papillomaviruses (HPV 16 or 18). Women who had taken the pill for 5-9 years were three times more likely than non users to develop cervical cancer. Women who had taken the pill for over 10 year were four times as likely to develop the disease. These risks were not affected by age of first use or time since first/last use. In a study of 889 women who died from cancer, Vessey et al (2003) found that, although oral hormonal contraceptives increased the risk of cervical cancer, they decreased the risk of endometrial and ovarian cancers. Barrier contraceptives such as condoms and intrauterine contraceptive devices do not appear to be factors in cancer initiation or development.
- Smoking: Several studies have shown that smoking is an independent risk factor for CIN and invasive cervical cancer as it is for many other epithelial cancer. It has even been suggested that passive smoking can increase the risk (Haverkos et al 2003). Nicotine products have been demonstrated in cervical mucus where they may act as a co carcinogenic agent. The polycyclic aromatic hydrocarbons in cigarette smoke form damaging adducts with DNA in the cervical epithelial cells which could result in mutation and neoplastic change (Simons et al 1994, 1995). There is some evidence that cigarette smoke may interact with human papillomavirus DNA to produce malignant transformation of epithelial cells.
- Immunological status: The concept that immune surveillance may be one of the major natural means of controlling tumour growth is supported by the fact that the prevalence of CIN in allograft recipients, cancer patients and HIV positive women. These groups of women have impaired T lymphocyte responses which may affect their ability to mount an adequate immune response against the foreign antigens on the cancer cells so that they are unable to eliminate or destroy them .
- Microbiological organisms: A range of microorganisms have been implicated in the past in the carcinogenic process including trichomonas vaginalis, herpes genitalis and chlamydia. The most recent studies indicate that the human papillomaviruses are the key agents in the aetiology of cervical cancer and its precursors.