Women’s Health




Crush cervical cancer
– make prevention a priority
 

Cervical cancer has a high mortality, particularly in resource poor countries, yet the disease can be prevented with HPV vaccines and routine Pap smear screening. As the incidence of cervical cancer continues to increase in the Middle East, it is clear there is a need for greater awareness among healthcare practitioners, parents and ministries of health to do what they can to reverse this trend – be it advising their patients, ensuring their teenage daughters are vaccinated or implementing a nationwide Pap smear screening programme and ensuring school girls are routinely inoculated with HPV vaccine. Middle East Health reports.

Cervical cancer is preventable, yet it is the second largest cause of mortality among women in the Middle East and the incidence of the disease appears to be increasing. In an effort to reverse this trend several specialists in the region are calling for greater awareness of the disease among primary healthcare practitioners, the implementation of screening programmes by government bodies and for greater public awareness of the disease.

Although recent incidence figures aren’t readily available for countries in the Middle East, worldwide there an estimated 500,000 cases a year, with approximately 270,000 deaths per year due to cervical cancer. Extrapolating these figures indicates that around 750 women die each day from the disease worldwide and an estimated 25 women die each day in the Middle East from the disease.

The figures should serve as a wake-up call to doctors, women, parents and ministries of health that this disease, which is fundamentally preventable, is a major cause of mortality.

Interestingly, there is a strong correlation between the incidence of cervical cancer and a country’s Gross Domestic Product (GDP), with around 83% of global cervical cancer cases occurring in resource-poor countries.

What is cervical cancer?


What exactly is cervical cancer? The US National Cancer Institute (NCI) defines it as a cancer that forms in tissues of the cervix. It is usually a slow-growing cancer that may not have symptoms, but can be found with regular Pap smear tests (a procedure in which cells are scraped from the cervix and studied under a microscope). Cervical cancer is almost always caused by human papillomavirus (HPV) infection.

The disease begins on the surface of cervix – the pre-invasive (or pre-cancer) stage. If not treated it can invade more deeply into the tissue of the cervix and becomes invasive cervical cancer and is classified in various stages depending on how deeply the cancer has penetrated the tissue and to what extent it has spread.

Human papillomavirus


There are more than 100 types of HPV – 40- 50 of which infect humans. Around 30 of these can infect the genital area.

HPV is very common and highly contagious. It is spread by sexual activity and skinto- skin contact in the genital area. HPV types 16, 18, 31, 33, and 45 are considered high risk and have been shown to be responsible for about 85% of cervical cancers. Types 16 and 18 alone are thought to be responsible for about 70% of cervical cancers.

The other HPV types cause warts on the body. Most genital warts are associated with HPV types 6 or 11.

Most HPV infections are asymptomatic or subclinical and will clear up in a matter of months with no treatment. However, persistent infection with high-risk types of HPV is considered the most important risk factor for cervical neoplasia. High-risk types are also known to cause anal or penile cancer in males – typically homosexuals.

Dr Quek Swee Chong, Senior Consultant and head of the pre-invasive and screening unit at KK Women’s and Children’s Hospital, Singapore, speaking to journalists in Dubai in April, said around 80% of women worldwide can expect to get an HPV infection at some point in their lives. “In many cases it will clear up within months without the woman ever knowing she had an infection.”

Dr Diane Harper, director of the Gynecologic Cancer Prevention Research Group at the University of Missouri, United States, and a lead researcher in the development of two HPV vaccines, was quoted as saying during a presentation last year at the 4th International Public Conference on Vaccination, in Reston, Virginia, US that 70% of all HPV infections generally resolve themselves without treatment within a year. Within two years, the number climbs to 90%. Of the remaining 10% of HPV infections, only half will develop into cervical cancer.

Risk factors


There are several risk factors for cervical cancer. The US NCI lists the following:

● HPV infection: HPV is the cause of nearly all cervical cancers.

● Lack of regular Pap tests: Cervical cancer is more common among women who don’t have regular Pap tests.

● Smoking: Among women who are infected with HPV, smoking cigarettes slightly increases the risk of cervical cancer.

● Weakened immune system: Infection with HIV or taking drugs that suppress the immune system increases the risk of cervical cancer.

● Sexual history: Women who start sex at a young age and who have had many sexual partners have a higher risk of developing cervical cancer. Also, a woman who has had sex with a man who has had many sexual partners may be at higher risk of developing cervical cancer. In both cases, the risk of developing cervical cancer is higher because these women have a higher risk of HPV infection.

Dr Chong noted, however, there should be no stigma attached to being diagnosed with an HPV infection as it does not necessarily mean the women has had multiple sexual partners. “It can take just one sexual activity to transfer the virus.”

● Using birth control pills: Using birth control pills for a long time (5 or more years) may slightly increase the risk of cervical cancer among women with HPV infection. However, the risk decreases quickly when women stop using birth control pills.

● Having many children: Studies suggest that giving birth to many children (5 or more) may slightly increase the risk of cervical cancer among women with HPV infection.

Symptoms

Unfortunately early stage cervical cancer does not show symptoms. Women with advanced cervical cancer may experience the following symptoms.
● Bleeding between regular menstrual bleeding
● Bleeding after sexual intercourse
● Menstrual bleeding that lasts longer and is heavier than previous bleeding
● Bleeding after menopause
● Increased vaginal discharge
● Pelvic pain
● Pain during sex

Prevalence Of cancers among women worldwide, cervical cancer is the fifth biggest killer, according the World Health Organisation. The cancer with the highest mortality is breast cancer, followed by lung, stomach, colorectal and cervical cancers.

“Worldwide, breast cancer ranks as the number one cancer, however in resource poor countries cervical cancer is number one,” Dr Chong pointed out, adding that some 83% of cervical cancer cases occur in resource poor countries, largely in the southern hemisphere. “The reason for this is that women in these countries do not have access to regular Pap smear tests. In Europe and the United States most women do have regular Pap smears and the disease is detected early and successfully treated.”

In the UAE, accurate figures of the prevalence of cervical cancer are difficult to obtain as there is no central cancer registry. Speaking to Middle East Health Dr Saad Ghazal-Aswad, a senior consultant gynaecological oncologist and chairman of the Obstetrics and Gynaecology Department at Tawam Hospital, Al Ain, UAE, said that he had noticed a significant increase in the incidence of cervical cancer over the past 10 years.

“When I started working at Tawam hospital in the late 1990s I used to see one cervical cancer case every month and one pre-invasive case about every 2 weeks. Now I see about 75- 100 cases per year [about 8 cases per month], although these cases also include lower genital tract neoplasia,” he said.

“My colleague in Saudi Arabia has experienced a similar increase,” he noted. According to Dr Falah Al Khatib, a radiation oncologist at Tawam Hospital, there were 41 cases of cervical cancer among UAE nationals in the three-year period between 1999 – 2001. It was highest among women between the ages of 40-49, followed by women in the 50-59 age group. Sixty eight percent presented with locally advanced disease (stage IIb - Stage IVa). Widespread metastases were observed in 7%.

Treatment

Standard treatments for cervical cancer depend of the extent and stage of the cancer and can involve surgery, radiotherapy or chemotherapy.

Following an abnormal Pap smear a colposcopy is performed. Colpscopy is a procedure where the cervix is illuminated and magnified for diagnosis. If the disease is at the pre-cancer stage it can be treated with minor surgery and treatment is usually very successful.

If the cancer is at stage 1 major surgery is required, which can range from total hysterectomy to radical hysterectomy and even pelvic exenteration, where the cervix, vagina, ovaries, and nearby lymph nodes are removed.

At Stage 2, 3 or 4 cervical cancer is inoperable and radiotherapy or chemotherapy is required. “However this is often just palliative care, as there is no cure,” noted Dr Chong.



Unfortunately, most cervical cancers are detected at an advanced stage according to Dr Chong. Most women who have cervical cancer have not had Pap smear tests. Dr Aswad corroborated this, saying in his experience most cases of cervical cancer in the UAE were presented at an advanced stage.

● The US NCI provides a comprehensive cervical cancer treatment PDQ (Physician Data Query) for healthcare professionals online: www.cancer.gov/ cancertopics/pdq/treatment/cervical/HealthProfessional

Prevention

Prevention is better than cure (or treatment) as the old adage goes ... and cervical cancer can be prevented.

Dr Chong emphasised: “It is the only cancer to affect women that can be truly prevented.”

There are two levels of prevention: Primary prevention through the abstinence of sex and inoculating against HPV with vaccines before sexual activity begins. Secondary prevention can be provided through regular Pap smears, early detection and treatment.

HPV vaccines

There are two HPV vaccines available. Cervarix by GSK (Glaxo Smith Kline) and Gardasil by MSD (Merck Sharp & Dohme). Both are effective against HPV types 16 & 18, responsible for about 70% of cervical cancers. Cervarix has been shown to provide some protection against types 31, 33, & 45 responsible for around a further 15% of cervical cancers. Gardasil is also effective against HPV types 6 & 11, which can cause genital warts and there is evidence that it protects againsts an additional 10 oncogenic HPV types that represent a further 20% of cervical cancer cases.

For these vaccines to be effective they should be given to women before they begin sexual activity and it is generally recommended they be given between the ages of 9 and 26 years. The US FDA approved Gardasil for use in females ages 9 to 26 and approved Cervarix for use in females ages 10 to 25. The licensing varies from country to country.

“The younger the person the stronger their immune reaction,” said Dr Aswad. “So it is better to give the vaccine at a younger age when they can develop a strong immunity to the virus.”

It is recommended that the vaccine is given in three doses over six months. Some countries have recently included either Cervarix or Gardasil in their routine vaccination programmes. In most countries in the Middle East this remains under discussion. However, the emirate of Abu Dhabi has decided to routinely inoculate all national girls at 17 years of age.

In the absence of the HPV vaccine being included in a ministry of health-driven vaccination programme the responsibility falls on doctors – primary health care practitioners, paediatricians and gynaecologists – to inform parents about the vaccine and urge them to have their daughters vaccinated before they become sexually active, said Dr Chong.

The duration of immunity provided by the vaccines is not yet known. Research is being conducted to find out how long protection will last. Phase III clinical trials have shown that Gardasil and Cervarix can provide protection against HPV16 for 4 years. Smaller studies have suggested that protection is likely to last for longer than 4 years, but it is not known if protection conferred through vaccination will be lifelong. Dr Chong noted that MSD and GSK predict that immunity could last 15-20 years.

The US NCI notes that studies are being carried out to find out whether booster vaccines will be necessary to prolong the immunity.

Vaccination in males


Gardasil may reduce the risk of genital warts in males (HPV types 6 & 11 are responsible for up to 90% of genital warts) and the vaccine has been licensed for use in young males in a number of countries.

● See: Lowy DR, Schiller JT (May 2006). “Prophylactic human papillomavirus vaccines”. The Journal of clinical investigation 116 (5): 1167–73. doi:10.1172/ JCI28607. PMID 16670757 Both vaccines are believed to reduce the rates of penile and anal cancer in men, which is also caused by HPV.

Pap smears

Regular Pap smears are recommended (every one to three years) for all women who are sexually active and should begin at least a year after sexual activity begins. The Pap test is essential to detect cervical cancers and precancerous changes. By being tested regularly it is highly likely that in the event of the development of pre-cancer it will be detected early and easily treated

The Pap test is not perfect, but the disease develops slowly and in the event a single Pap smear provides a false negative, by having it performed regularly it should still show any abnormal state that may have developed, explained Dr Chong.

Current preventive vaccines reduce, but do not eliminate the chance of getting cervical cancer. Therefore, experts recommend that women combine the benefits of both programmes by seeking regular Pap smear screening, even after vaccination.

Screening

In developed countries, the widespread use of cervical Pap smear screening programmes has reduced the incidence of invasive cervical cancer by 50% or more.

In certain quarters in the Middle East there have been calls for governments to implement Pap smear screening programmes due to the apparent increasing incidence of cervical cancer and because in many cases it is presented as late stage cancer.



Dr Aswad noted that based on an analysis of the epidemiological data that was available for the incidence of cervical cancer in the UAE, he and other experts in the field were of the opinion that there were enough cases to warrant a comprehensive government- driven screening programme for cervical cancer in the UAE.

At a National Workshop for Cervical Cancer Prevention in Abu Dhabi in 2004, senior physicians in the UAE, including Dr Aswad, called on government to implement such a programme and drew up a report providing a comprehensive plan of action. However, a screening programme has yet to be implemented.

Vaccination programmes

National vaccination programmes with one or the other of the HPV vaccines have been introduced recently in a number of countries. The implementation of such a programme is a major undertaking on the part of government both financially and organisationally. Ideally the vaccine should be given to preteen or early teen age girls and should be done so while they are at school to facilitate the organisational success of the programme. At this stage in the GCC countries only the Emirate of Abu Dhabi has implemented a programme to vaccinate all 17-year-old national and non-national girls with the Gardasil quadrivalent HPV vaccine. In other emirates and countries in the region such vaccination programmes are apparently under discussion. In the interim doctors are urged to inform parents about the benefits of the vaccination.

In Australia, commencing in 2007, the federal government began funding a voluntary programme to make the Gardasil vaccine available free of charge to women aged 12–26 for a period of two years, with an ongoing vaccination programme for 12- and 13-year-olds as part of the pre-existing high school vaccination programme.

In the United Kingdom HPV vaccination with Cervarix was introduced into the national immunisation programme in September 2008, for girls aged 12–13 across the UK. A two-year catch up campaign started in Autumn 2009 to vaccinate all girls up to 18 years of age.

New Zealand, France, Sweden, South Korea, Romania and several other countries all have some form of state-funding for the vaccine enabling girls to be vaccinated for free or with state subsidy.

However, in some countries where there is no state subsidy the vaccines remain out of reach for many. For example, in Kenya, where Cervarix and Gardasil are approved, they cost in the region of 20,000 Kenyan shillings (about US$260), which is more than the average annual income for a family.

In conclusion

Speaking at a symposium at the 2nd annual Middle East Obs-Gyne Congress in Dubai in February this year, Dr Waleed Al Jassar, Assistant Professor of Gynaecology Oncology from the Faculty of Medicine at Kuwait University, said: “Perhaps it is because of the culture in the Middle East or perhaps it is because cervical cancer has no symptoms, but more attention needs to be given to this disease and its preventative measures.

“In the case of cervical cancer, we are faced with a deadly disease which results from an untreated virus, a virus that can be prevented with a vaccine.”

He called on doctors to gain a clear picture of how they can help women reduce the risk of contracting HPV and the resulting cancer. Also speaking at the symposium, Dr Muna El Kuwari, Director of Primary Healthcare for the UAE Ministry of Health, said: “With the advent of vaccines against cervical cancer, we now have powerful new tools to reduce cervical cancer and save women’s lives.”

Dr Chong emphasised that there was a major effort worldwide, which is gaining momentum, to increase awareness of cervical cancer, “because we have the ability to prevent it”.
 

Further Reading

The following papers are Open Access. No subscription is required.

■ Are treatments for cervical precancerous lesions in less-developed countries safe enough to promote scaling-up of cervical screening programs? A systematic review. Eric Chamot et al BMC Women’s Health 2010, 10:11 doi:10.1186/1472-6874-10-11

■ Prevalence of various Human Papillomavirus (HPV) genotypes among women who are subjected to routine Pap smear test in Bushehr city (South west of Iran)2008-2009 Keivan Zandi et al Virology Journal 2010, 7:65 doi:10.1186/1743-422X-7-65

■ A randomized controlled trial of Human Papillomavirus (HPV) testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial) Gina S Ogilvie et al BMC Cancer 2010, 10:111 doi:10.1186/1471-2407-10-111

■ Type-specific incidence, clearance and predictors of cervical human papillomavirus infections (HPV) among young women: a prospective study in Uganda Cecily Banura et al Infectious Agents and Cancer 2010, 5:7 doi:10.1186/1750-9378-5-7


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ate of upload: 20th June 2010

                                  
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