About cervical cancer
Cervical cancer quick facts
Cervical cancer basics
What is the burden of cervical cancer in low-resource settings?
What causes cervical cancer?
How is HPV transmitted?
What types of HPV are cancer-causing?
How can cervical cancer be prevented?
What vaccines against HPV infection are available?
What do HPV vaccines protect against?
For how long will the HPV vaccine provide protection?
Are HPV vaccines safe?
Are HPV vaccines safe for pregnant women?
At what age should girls or young women be vaccinated against HPV?
Should males be vaccinated?
Are there HPV vaccination programs in high-resource countries?
Are there HPV vaccination programs in low-resource countries?
Can HPV vaccination programs be cost-effective in low-resource countries?
What HPV vaccines might be available in the future?
Screening and treatment
Is cervical cancer screening still needed in addition to HPV vaccination programs?
What screening methods are available, and which are recommended for low-resource settings?
What precancer treatment methods are available for low-resource settings?
What is the "screen-and-treat" approach?
How will screening change in the age of HPV vaccination?
Promoting comprehensive cervical cancer prevention programs
What are the key points for developing comprehensive cervical cancer prevention programs?
What can facilitate community and government support for cervical cancer prevention programs?
Cervical cancer basicsWhat is the burden of cervical cancer in low-resource settings?
- Cervical cancer takes the lives of more than 270,000 women every year, over 80 percent of them in less developed countries.
- The highest incidence and mortality rates are in sub-Saharan Africa; Latin America and the Caribbean; and South and Southeast Asia. Even though industrialized countries have experienced dramatic declines, the death rate is still high in regions with poor access to health care or other barriers to cervical cancer screening and early treatment.
- The loss of mothers, grandmothers, and other essential family members who take care of children, provide income, and work in their communities causes great personal suffering and also results in significant economic hardship.
- Human papillomaviruses (HPV) are the cause of virtually all cervical cancers.
- Papillomaviruses are tissue-specific DNA viruses that are easily transmissible and highly prevalent.
- HPV types 16 and 18 cause approximately 70 percent of cervical cancer cases worldwide.
- The vast majority of HPV infections are transient: they clear as a result of natural immune responses. However, precancer can develop if infection persists, and precancerous cells can become cancerous over time.
- HPV lives in the skin, not in the body fluids (unlike HIV). HPV infection is sexually transmitted, but penetrative sex is not required for infection: skin-to-skin genital contact also can result in infection.
- HPV is highly transmissible, with peak incidence among those who have recently become sexually active. HPV is the most common sexually transmitted infection, with about 630 million people believed to be infected with HPV worldwide. Globally, 50 to 80 percent of sexually active women are infected by HPV at least once in their lives.
- In the United States, studies have shown that about 40 percent of young women become infected with HPV within three years of sexual debut.
- While most people are infected with HPV sometime in their lives, only a small percentage will develop cancer. Additional factors increase the risk for progression to cervical cancer, such as: early age at first sexual intercourse, high number of pregnancies, multiple sexual partners, smoking, long-term use of hormonal contraceptives, and infection with HIV.
- Human papillomaviruses comprise a large family of viruses, with more than 100 types known. Some infect the genital tract and of these, some have a high potential for causing cancer (oncogenic types), whereas others cause non-cancerous conditions.
- Oncogenic HPV types cause a variety of anogenital and other cancers, such as oral cancer.
- Nononcogenic HPV types cause genital warts, abnormal cervical cytology, recurrent respiratory papillomatosis, or infections that go unnoticed and eventually clear up.
- While HPV 16 and 18 are associated with about 70 percent of all cervical cancer cases, at least 11 other HPV types cause cancer, though less commonly. Among these, HPV 45 and 31 each account for about 4 percent of cervical cancer cases.
- HPV vaccination given to young adolescent girls prior to sexual debut can lower the risk of cervical cancer by preventing infection with HPV 16 and 18, the most common infections leading to cervical cancer.
- Eliminating the risk factors mentioned above can decrease the probability that infections will progress to cancer.
- Cervical cancer also can be prevented if precancerous lesions are identified early through screening and then treated. Early treatment is usually highly effective.
- Two vaccines against HPV have been licensed in more than 100 countries worldwide: Merck & Co., Inc.’s Gardasil® and GlaxoSmithKline’s Cervarix®.
- Both vaccines consist of virus-like shells containing no DNA, so they cannot cause HPV infection. The vaccines also include compounds called adjuvants that stimulate the immune system.
- Both Gardasil and Cervarix protect against the most common cancer-causing types of HPV, types 16 and 18. Gardasil also protects against HPV types 6 and 11, which cause about 90 percent of genital warts.
- Both vaccines are given in a series of three 0.5-mL intramuscular injections over six months, with slightly different schedules.
- Efficacy in preventing precancerous lesions caused by HPV 16 or 18 is very high for both vaccines—greater than 92 percent in women who have not been previously infected with these viral types. Note that this efficacy applies to the 70 percent of cancers caused by HPV 16 or 18, not all cervical cancer.
- The vaccines are much less effective in women who have already been exposed to one or both of these HPV types.
- Both Gardasil and Cervarix appear to offer some protection against cancer-causing HPV types that are not targeted by the vaccines, mainly against type 31, which is related to type 16. Cervarix has also shown efficacy against type 45. However, protection does not reach the levels demonstrated for types 16 and 18.
- Published clinical trial results show that HPV vaccines are efficacious in preventing infection and high-grade lesions for at least five years (Gardasil) to more than six years (Cervarix) and preliminary results from a trial of the HPV 16 component of Gardasil indicate that it is efficacious for up to 8.5 years.
- This is the duration of protection reported to date, based on follow-up data from the major clinical trials. It is encouraging that protection has not been shown to diminish over time, and the vaccines may prove to be effective for much longer.
- Definitive results will become available only when clinical trial participants have been followed for a longer period of time.
- In clinical trials for both HPV vaccines, low rates of side effects were associated with vaccination.
- Common side effects included injection-site pain, swelling, bruising, and/or irritation. Other frequent effects were headache, fever, nausea, vomiting, muscle aches, and fainting. Most side effects were mild to moderate and of short duration— from several hours to a few days.
- Some serious side effects were reported, such as severe headaches and gastroenteritis, but similar rates were reported in those who received control injections.
- After more than five years of follow-up, no deaths have been shown to have been caused by HPV vaccines.
- The US Centers for Disease Control and Prevention and the Medicines and Healthcare products Regulatory Agency in the UK have concluded that the vaccines are safe and effective and that the benefits continue to outweigh risks.
- For further information on vaccine safety, please refer to the Outlook newsletter.
- Manufacturers of both vaccines, along with regulatory agencies, recommend against vaccinating pregnant women because no randomized controlled trials have been done to formally assess safety in this population.
- Among women who became pregnant in the clinical trials (in spite of requirements to avoid pregnancy), researchers found no significant differences between outcomes in the vaccine and the control groups in overall analyses.
- However, when subsets of pregnancies that began around the time of vaccination were analyzed, small increases in miscarriage and congenital anomaly rates were seen in some trials. The differences between rates in vaccine and control groups were not statistically significant, but investigators are continuing to recommend against vaccination during pregnancy until more data are available.
- For further information, please refer to the Outlook newsletter.
- The HPV vaccines have been licensed by many country regulatory agencies worldwide, and the ages approved for use vary, although age 9 is the youngest approved.
- Many countries have adopted policies that support vaccination of female adolescents before sexual debut, around ages 9 to 13, as recommended by the World Health Organization.
- Although vaccination even earlier in life poses no theoretical risk, no studies have yet been published to support vaccination of younger girls or infants.
- While regulatory bodies in many countries have approved the use of the vaccines in women up to their mid-twenties and beyond, thus far it is not recommended that public health programs—especially those in the developing world—allocate resources to vaccinate sexually experienced, older women, since both vaccines show much lower efficacy after HPV infection. Rather, cervical screening is considered the best approach for this group.
- Boys can become infected with HPV, they can infect female partners, and they can develop HPV-associated diseases such as penile, anal, and oral cancers or genital warts.
- Some experts believe that vaccinating both males and females would benefit women because women are infected by male sexual partners, but computer models suggest that this strategy may not be cost-effective unless vaccine coverage of girls is low.
- Because cervical cancer represents the greatest burden of disease from HPV, most public health experts recommend that efforts concentrate on vaccinating girls and young women.
- Several industrialized countries have introduced government-funded HPV vaccination programs and in other countries the vaccines are approved and available in the private sector.
- In the United States, while vaccination is not covered by a national program, it is recommended for all girls 11 to 12 years of age, and may be started in girls as young as 9 years.
- The UK began a national program in September 2008 for all 12- to 13-year old school girls.
- In 2008, Australia started a national school-based program for girls age 11 to 12,
- In 2006, PATH began a program of vaccination demonstration projects in India, Peru, Uganda, and Vietnam that were designed to simulate national HPV immunization programs and to provide a basis for future policy decisions.
- These demonstration projects have shown that HPV vaccination is acceptable and feasible in these areas, and that high coverage can be attained.
- Some other low-resource countries have initiated or are planning to initiate HPV vaccination programs, but they have not yet published their experience or data.
- For further information on vaccine safety, please refer to the Outlook newsletter.
- Until prices come down or less expensive vaccines enter the market, HPV vaccination programs in many countries will be possible only with substantial subsidies.
- Vaccination programs will include costs in addition to vaccines; for example, costs for equipment, personnel, clinic space, and capital costs such as cold chain systems and delivery vehicles.
- Because most low-resource settings do not routinely vaccinate older children and adolescents, HPV vaccination programs will need to be integrated into existing immunization programs and other outreach activities such as Child Health Days, or new systems will need to be created.
- For further information, please refer to the Outlook newsletter available at: http://www.rho.org/ccresources.htm#outlook
- A key goal for the future is to develop preventive vaccines that are more suitable to resource-limited areas. Desirable characteristics for use in these areas are lower cost, efficacy with fewer doses, efficacy when given orally or nasally, and stability at a range of temperatures.
- Vaccines that prevent infections with more oncogenic HPV types are also needed, and are now in development.
- Currently, no therapies are available for eliminating persistent HPV infections, but researchers are working on such vaccines.
- Other therapeutic vaccines could potentially eliminate preexisting lesions and tumors by generating immunity against HPV-infected cells expressing viral DNA or proteins.
Screening and treatment
- Although HPV vaccines are expected to significantly reduce the risk and incidence of cervical cancer, they will not replace screening; rather, use of the vaccines along with screening will maximize overall effectiveness.
- Screening is needed for the millions of women age 30 or older in whom HPV infection has likely occurred if they have been sexually active sometime in their lives.
- Current vaccines target only the two HPV types known to cause 70 percent of cervical cancer, so screening for lesions and cancer caused by other types must continue.
- It will also take time for HPV vaccination programs to attain high coverage rates.
- Until new vaccines can prevent infections by oncogenic types in addition to types 16 and 18, and until vaccines are 100 percent effective and can confer lifelong immunity, prevention programs must include screening.
- Screening of sexually active or formerly active women can determine whether they are at risk of developing cervical cancer. The goal of screening is to find and treat cervical precancer before it becomes invasive cancer. Success rates are high when the disease is treated early.
- Cytologic (Pap) tests examine cells gently scraped from the cervix.
- Pap tests have reduced cervical cancer incidence and deaths dramatically in industrialized countries, but maintaining cytology laboratories country-wide in low-resource regions is not feasible because of the lack of supplies, trained personnel, equipment, quality control, health care infrastructure, and effective follow-up procedures.
- Even where it is feasible and in broad use, cytology has low sensitivity. This means that the test misses many precancer and cancer cases, and relies on repeated tests every few year. This is not feasible in low-resource areas.
- Visual inspection procedures are used to examine the surface of the cervix after applying a staining solution.
- Visual inspection with acetic acid (VIA) has sensitivity comparable to or greater than that of Pap testing. VIA involves swabbing the cervix with three to five percent acetic acid (vinegar) during a speculum exam and observing the cervix. If well-defined white areas appear, the test is considered positive for precancerous cell changes or early invasive cancer.
- Visual inspection of the cervix is ideal for low-resource settings because it requires simple equipment, relatively brief training, and can be performed by midlevel health personnel. Results are immediately available and treatment can be provided at the same visit (see the "Screen-and-treat" section below), thus reducing loss to patient follow-up.
- Research over the past 10 years has shown that visual inspection techniques work as well as, or better than, the much more complex Pap testing.
- HPV DNA tests detect the genetic material of oncogenic viruses in samples collected from the vagina or cervix.
- Molecular tests detect DNA from cancer-causing HPV types in vaginal or cervical smears collected using a small brush or swab. Trained providers must collect cervical samples, but women can collect vaginal samples themselves.
- HPV DNA testing is particularly valuable in detecting high-grade precancerous lesions in women older than 30. HPV infections in women younger than 30 are likely to be transient, so testing young women (with HPV DNA tests or other screening methods) can lead to unnecessary referrals or treatment of lesions that would regress spontaneously.
- Current approved HPV DNA tests are much more sensitive than visual inspection methods or cytology, but so far are unaffordable in low-resource areas.
- The careHPV test (Qiagen, Inc.) detects DNA from 14 cancer-causing types of HPV. Developed and field-tested for use in low-resource settings, careHPV test results are available in about 2.5 hours without extensive laboratory facilities. The careHPV test should become available commercially in 2011 or 2012. If it proves to be simple, rapid, accurate, and affordable, it may become a suitable screening tool for low-resource settings.
- Women with precancerous cervical lesions who receive treatment have an excellent chance of avoiding progression to cervical cancer. Several treatment methods exist, and one, cryotherapy, is very suitable for low-resource settings.
- With cryotherapy, the affected area of the cervix is frozen with a cold probe, which destroys the precancerous cells. Both the equipment and procedure are relatively simple, and if the use of cryotherapy is restricted to cases where lesions are small (about 20 millimeters) and entirely visible (do not extend into the cervical canal), treatment efficacy is 85 to 95 percent.
- There are some cases where cryotherapy is not indicated; for example, when the affected area is too large or is not reachable by the cold probe, or there is suspicion of invasive cancer. These cases must be referred for a higher level of care.
- A promising strategy is becoming available in some low-resource settings—the “screen-and-treat” or “single-visit approach.” In this method, women who test positive on VIA or HPV DNA tests do not undergo further diagnostic testing; instead, they receive treatment triage and then are treated immediately or shortly after screening. If treatment is offered at the same visit, it is known as a single-visit approach.
- The most efficient and effective strategy for finding and treating precancerous lesions in low-resource settings is screening with either VIA or HPV DNA testing, and treating immediately using cryotherapy, without further diagnostic confirmation.
- Once HPV vaccination gains momentum and more sensitive tests than Pap or VIA are in widespread use, it is likely that the screening strategies common today, such as Pap tests repeated every two to five years as in some high-resource countries, will change.
- One proposed scenario is to vaccinate prior to sexual debut, then screen only a few times when a woman is in her 30s and 40s, using HPV DNA testing (or other future molecular tests that may give a better indication of which women are at highest risk of precancer). Such a strategy would be feasible in low-resource settings and would save considerable costs in wealthier countries.
- In countries that do not yet have screening programs, policymakers may consider initiating screening of women aged 30 and older at least once or twice in their lifetimes, in conjunction with vaccination of girls and young women who are not yet sexually active.
Promoting comprehensive cervical cancer prevention programs
- HPV vaccination cannot reach people in low-resource settings unless the vaccines become affordable, health infrastructures can support vaccination programs, and governments institute national HPV immunization programs.
- Prevention strategies must include screening for cervical lesions or HPV infection among adult women, because vaccines do not protect against all cancer-causing types and because many women are not vaccine candidates.
- Integrating cervical cancer prevention programs with other health interventions will lead to better care for girls and women and can improve cost-effectiveness.
- Preventing cervical cancer is an integral part of the broader agenda of meeting women's health needs, and it is essential for women’s rights and health equity.
- Accurate information is essential for improving the understanding of HPV infection and cervical cancer among health care workers, educators, policymakers, parents, and patients. Without such understanding, these groups are unlikely to support interventions.
- As with all health education, understanding audiences and crafting appropriate messages, based on cultural background and educational levels, is crucial. For example, some vaccination programs in low-resource countries found that for the general public, using the phrase "cervical cancer vaccine" best communicated the benefits of the intervention, while health professionals understood "HPV vaccine."
- Because health care providers are often the primary source of information for parents and adolescents, providers need to be educated about how to help patients understand the advantages offered by both screening and vaccination.
- In both high- and low-resource countries, it is unclear which types of providers will deliver the vaccines—community health workers, general physicians or nurses, pediatricians, nurse midwives, or obstetricians and gynecologists. Therefore, training will be needed for any of these providers involved in implementing HPV vaccination programs.