Prevention of cervical cancer and other HPV-related lesions through vaccination

CERVICAL cancer is the second most common cancer among women worldwide and is the leading cause of death in developing countries. Five hundred thousand women are diagnosed annually, and every two minutes a woman dies of cervical cancer somewhere in the world. It is projected that by 2050 more than one million new cases of cervical cancer will be detected each year. Despite the impact of screening worldwide, women continue to be at risk.

The highest burden of disease (up to 80 per cent) occurs in developing countries where there is a lack of effective screening programmes. Every year across Africa 79,000 women are diagnosed with cervical cancer and 62,000 women die from the disease. The highest mortality rate is seen in Sub Saharan Africa, with a rate of 55.6/100,000 in Tanzania, and lowest in North Africa (Morocco) with a rate of 10.7/100,000. In addition to Sub-Saharan Africa, Melanesia, Latin America, the Caribbean, South Central Asia and South East Asia belong to the region with the highest incidence rate.

The age-specific rate in the Caribbean is 33.5/100,000 with a rate of 27.9 per 100,000 in Jamaica. The death rate in Jamaica is 15.8 per 100,000. High mortality rates are seen in Haiti (48.1 per 100,000) with lower rates in Brazil (10.2 per 100,000) and Argentina (7.8 per 100,000). The lowest rate is seen in Arabia (now Iran) with a rate of 0.1/100,000. The regional variations exist because of the availability and extent of cervical screening programmes.

The incidence in North America is low compared to the global average (12.4 per 100,000): Canada and the USA have an incidence of 7.7 per 100,000. Local variations in the USA could reflect variability of access to screening. The low incidence and mortality in North America may reflect the availability of well-established opportunistic screening programmes. Fifty-five million cervical screening tests are performed every year in the USA, with up to 6.9 per cent yielding positive or inconclusive results. Despite the impact of screening, each year 14,500 women are diagnosed in North America with cervical cancer, and 6,000 will die from the disease.

The cause of cervical cancer is the human papilloma virus (HPV) which is sexually transmitted and is the most common genital infection worldwide. Over 100 HPV types are characterised and 40 types infect the genital tract. The eight most common types are HPV 16, 18, 45, 31, 33, 52, 53 and 35, and these account for 90 per cent of cervical cancer cases worldwide. HPV 16 and 18 together account for 70.7 per cent of cervical cancer cases, and the inclusion of 45 and 31 raises the figure to 80.3 per cent of cases. Exposure to HPV occurs once sexual activity begins. There is no cure for HPV, and one cannot predict who will develop persistent infection and with which HPV type.

On the whole, HPV infection is clinically silent and self-limiting. Some women remain persistent carriers of the viral infection and become at high risk of progression to pre-cancer and cancer of the cervix, vulva, vagina and anal canal. HPV may also cause cancer of the penis and anal canal in HPV- infected men. It also causes cancer at other sites. Women have a greater risk of HPV infection than men, and carry the greatest disease burden from HPV. Women who are infected with HPV are very likely to infect their sexual partners, who may then transmit it further to new sexual partners.

Secondary prevention of cervical cancer by doing Pap smears annually from age 21 is the standard recommendation for all women, whether or not they are sexually active. Primary prevention of cervical cancer by the use of vaccination is the way forward. Two vaccines are locally available and are currently being used widely. GARDASIL®9 protects against genital warts caused by HPV 6 and 11, and also gives protection against HPV 16, 18, 31, 33 45 52 and 58. It is given in three doses — the second is given two months after the first, and the third is given six months after the first dose. It is recommended from age 10 to age 26. The vaccine Cervarix® is effective in reducing persistent infection from HPV types 16, 18, 45 and 31, and over several years will reduce the incidence of cervical cancer and other HPV-related cancers of the genital tract in women. The vaccine is given in three doses in the muscles of the arm over a period of six months. The second injection is given one month after the first, and the final one is given five months after the second one.

The vaccines have been shown to be safe, effective and well tolerated by women and children from age 10 to age 65. In young girls it has been shown that two doses of the vaccine provide added lifetime coverage. The vaccines give good long-term protection against both squamous cell and adenocarcinoma of the cervix. Vaccines have not been associated with any serious adverse effects. These vaccines are FDA-approved and are also approved on the European market.

Although cervical cancer screening has greatly reduced morbidity and mortality, it has its limitations. It does not prevent HPV infection or development of early pre-cancerous changes in the cervix. In some cases the disease progresses quickly and may not be detected in time. Cervical cancer screening is not widely available in all countries.

Vaccination provides primary prevention against cervical HPV infection, which causes cervical cancer. However, vaccination does not protect against all HPV types, so screening is essential and must be continued. The best time to vaccinate is prior to the onset of sexual activity. It is important to note that women remain at risk of HPV infection throughout their sexually active lives, and can therefore benefit from vaccination. Women who have had the HPV infection or abnormal cervical changes on Pap smear should definitely be vaccinated. The abnormal changes should be treated and then vaccination should be undertaken to prevent recurrence from re-exposure to HPV.

Any impact of vaccination on cervical cancer rates will be seen in 15 to 20 years, with the full effect of vaccination on cancer rates in 30-50 years. HPV vaccine is a major advance in the prevention of cervical cancer but will not replace the need for other preventable strategies including routine cervical screening.

Dr Sharmaine Mitchell is a consultant obstetrician and gynaecologist and lecturer at the University of the West Indies, Mona.