Human Papillomavirus and Cervical Cancer |
Printer-friendly version (242k, Adobe Acrobat)
Back
Preventing Cervical Cancer
As mentioned above, HPV is the most prevalent sexually transmitted infection in the world. And, unlike other STDs such as gonorrhea or HIV/AIDS, use of condoms and other safe-sex practices may not be nearly as effective in preventing infection. This is because the papilloma virus lives in the skin (squamous) cells covering the pubic area (vulva and shaft of the penis) as well as the interior cells lining the vagina and cervix in women, and urethra and anus in both sexes. Condoms do not cover the entire shaft of the penis nor do they block contact with pubic skin. Therefore, during intercourse, even with a condom, skin cells containing HPV can come in contact with a woman’s vulva or vagina, enabling the virus ultimately to reach the cervix. In addition, the friction of sexual intercourse is believed to cause tiny, microscopic tears in the vaginal wall, making transmission far more likely. Moreover, even dead cells shed during intercourse can contain the virus and remain infective for days (Roden, Lowy and Schiller 1997).
Primary Prevention
The most effective way to prevent cervical and other genital cancers would be a vaccine. Individuals would need to be immunized at an early age before they are sexually active. The benefits of such a vaccine would be particularly significant in developing countries, where women’s healthcare services are minimal. Designing a vaccine, however, will not be easy because people’s immune response appears to be specific to the type of HPV. For example, a person protected against type 16 would still be at risk of infection with other cancer-inducing types, such as 18 or 33. There also appear to be subtypes or variants within type 16, and perhaps with other types as well. Finally, as mentioned above, the types of HPV associated with cervical disease vary by geographical area. With the increase in international travel, the various carcinogenic types soon will be spread throughout the world. Therefore, a vaccine with a mixture of several types would have to be created (Groopman 1999; Stewart et al 1996).
Despite these problems, safety testing of at least two vaccines that could protect women from cancer-linked papilloma viruses is underway. Estimates are, however, that it will be several years before either would be available, and many more years before they would be affordable in developing countries. Finally, there also are attempts to produce a therapeutic vaccine, one which would boost the immune system of someone who is already infected and cause the cancer to regress or even disappear. These vaccines are targeted to inactivate the E6 and E7 proteins, those viral proteins that block the action of the cell growth regulating proteins (Rb and p53) (Massimi and Banks1997).
Until such time that a protective vaccine is widely available, primary prevention must focus on continuing to change sexual practices and other behaviors that increase a person’s risk of becoming infected. Just as with the fight against HIV/AIDS, risk reduction counseling related to the risk factors listed above (Table 1) must be incorporated into all levels of the healthcare system, especially those dealing with young people. The messages must include alerting teenagers that practices designed to minimize the risk of STD or HIV/AIDS exposure (i.e., the use of male or female condoms) may not be as effective for HPV prevention.1 In addition, vigorous efforts to discourage adolescents, especially young girls, from starting smoking and initiating sexual activity must be widely and continuously disseminated.
Secondary Prevention
Although at present prevention of HPV infection is difficult, for women already infected the immediate need is:
to identify those with early, easily treatable precancerous lesions; and
to cost-effectively treat them before the lesions progress to cancer.
Since 1989, JHPIEGO has been exploring the feasibility of several low-cost alternatives for cervical cancer detection. Prominent among these is unmagnified (naked eye) visual inspection using a dilute solution of acetic acid (VIA). In March 1999, researchers from JHPIEGO and the University of Zimbabwe reported in The Lancet that the sensitivity (77%) and specificity (64%) of VIA are comparable to those of good quality Pap smears. This large-scale study, which involved more than 10,000 women attending primary healthcare clinics in Zimbabwe, confirmed the findings of similar studies in South Africa and India (Sankaranarayanan et al 1998). A second major finding from the Zimbabwe study was that nurse-midwives, who did all the VIA tests, quickly learned to competently perform them. This finding is important because the vast majority of developing country women who need to be tested live in areas where there are no doctors and where Pap smears may never be available. Furthermore, unlike Pap smears that require several days to a week to get the results back, with VIA the results are available immediately. As a consequence, these nurse-midwives were able to quickly and easily identify women with no disease, those with abnormal findings suitable for immediate treatment and those with very large lesions or advanced disease requiring referral.
With the establishment of VIA as an acceptable alternative to Pap smears (Kitchener and Symonds 1999), it is now possible to offer VIA with outpatient treatment of precancerous lesions at the same visit. For example, cryotherapy, which involves freezing the cervix with a liquid coolant such as carbon dioxide to destroy the abnormal cervical tissue, is highly effective. And cryotherapy has been used extensively throughout the world for more than 20 years (Cox 1999; Mitchell et al 1998; Olatunbosun, Okonofua and Ayangade 1992). Cryotherapy is also one of the easiest methods to learn and can be performed by nurses and other healthcare workers. In light of these promising epidemiologic studies and the availability of a simple, low-cost outpatient method of treatment, the opportunity to markedly reduce the incidence of cervical cancer globally is at hand. As the first step (Phase 1) in this process, JHPIEGO is conducting several safety, acceptability, feasibility and program effectiveness (SAFE) demonstration projects in separate regions of the world. These SAFE projects are needed to:
show that nurses and midwives can competently perform both VIA and cryotherapy in low-resource settings,
demonstrate that nurses and midwives can confidently treat or refer women with abnormal (precancerous) lesions, and
document the acceptability and feasibility of cervical cancer testing that is directly linked to immediate treatment.
We anticipate the results of these studies will show that well-trained nurses and midwives can quickly and easily identify patients who are appropriate for immediate treatment with cryotherapy or refer those requiring more aggressive treatment (or those with advanced disease). We also expect to learn that a test, treat or referral program is a safe, acceptable and feasible approach for preventing cervical cancer in low-resource settings. Finally, we anticipate identifying ways in which large-scale Cervical Cancer Prevention (CECAP) programs can be implemented nationally through a combination of individual and community education, participation by local nongovernmental organizations and women’s groups, and sponsorship by indigenous service organizations and clubs.
This practical approach to preventing cervical cancer has the potential to reduce disease progression and death in a majority of women who currently do not have access to Pap smears and physician-staffed services. Also, it has the potential to reduce referrals of women with early lesions to higher levels of the healthcare system as well as increase the chance of detecting invasive cancer at an earlier stage when it can be treated successfully. Finally, once a precancerous lesion is treated, a woman’s risk of developing an infection with other HPV types may be reduced for several years, while those women found to be normal may not need retesting for 5 or more years (Lonky et al 1997; Lonky et al 1999).
Summary
Human papillomavirus is the most prevalent STD in the world, occurring at some point in up to 75% of sexually active women. Nearly all cervical cancers are directly linked to previous infection with one or more of the oncogenic types of HPV. Other risk factors for cervical cancer include sexual activity at a young age, multiple sexual partners, immunosuppression and HIV infection. Lacking an appropriate vaccine for HPV, primary prevention of cervical cancer must focus on condom use and changing sexual practices as well as other behaviors that increase a person’s risk of becoming infected with HPV.
For women already infected with HPV, the immediate need is to identify those with early, easily treatable precancerous lesions and to treat these women cost-effectively before the lesions progress to cancer. Visual inspection using a dilute solution of acetic acid (VIA) has been established as an acceptable alternative to Pap smears. Therefore, it is now possible to offer VIA with cryotherapy, an outpatient treatment that uses a liquid coolant to destroy abnormal cervical tissue. Cryotherapy is highly effective and has been used extensively throughout the world for more than 20 years. Once a precancerous lesion is treated, a woman’s risk of developing an infection with other HPV types may be reduced for several years, while those women found to be normal may not need retesting for 5 or more years.
1 A recent case-control study, however, has shown that male condom use, which significantly decreases the amount of infectious virus deposited in the vagina during sexual intercourse, offers substantial protection (Wen et al 1999).
References
Cason J, P Rice and JM Best. 1998. Transmission of cervical cancer-associated human papilloma viruses from mother to child. Intervirology 41(4–5): 213–218.
Cox TJ. 1999. Management of cervical intraepithelial neoplasia. Lancet 353 (9156): 941–943.
Groopman J. 1999. Contagion. The New Yorker (13 September): 44–49.
Hanissian J. 1997. Emerging HPV vaccines. Infect Med 14(4): 266,273–275, 300.
Judson FN. 1992. Interactions between human papillomavirus and human immunodeficiency virus infections. Scientific Publications 119: 199–207.
Kitchener HC and P Symonds. 1999. Detection of cervical intraepithelial neoplasia in developing countries. Lancet 353: 3.
Lonky NM et al. 1999. Reducing the incidence and mortality of cervical cancer (part 1). OBG Management (November): 26–45.
Lonky NM et al. 1997. Selecting treatments for cervical disease (part 2). OBG Management (January): 60–70.
Magnusson P, P Sparen and U Gyllensten. 1999. Genetic link to cervical tumors. Nature 400: 29–30.
Massimi P and L Banks. 1997. Repression of p53 transcriptional activity by the HPV E7 proteins. Virology 227(1): 255–259.
McDonald C. 1999. Cancer statistics, 1999: Challenges in minority populations. CA Cancer J Clin 49(1): 6–7.
Mitchell MF et al. A randomized clinical trial of cryotherapy, loop electrosurgical excision and laser vaporization for treatment of squamous intraepithelial lesions of the cervix. Am J Obstet Gynecol 92: 737–744.
Moscicke AB et al. 1999. Risk factors for abnormal anal cytology in young heterosexual women. J Cancer Epidemiol Biomarkers Prev 8(2): 173–178.
Olatunbosun OA, FE Okonofua and SO Ayangade. 1992. Outcome of cryosurgery for cervical intraepithelial neoplasia in a developing country. Int J Gynaec Obst 38: 305–310.
Palank C. 1998. An introduction to colposcopy concepts, controversies and guidelines. ADVANCE for Nurse Practitioners 6(10): 45–50, 91.
Roden RB, DR Lowy and JT Schiller. 1997. Papillomavirus is resistant to desiccation. J Infect Dis 176(4):1076–1079.
Sankaranarayanan R et al. 1998. Visual inspection of the uterine cervix after application of acetic acid in the detection of cervical carcinoma and its precursors. Cancer 83: 2150–2156.
Stentella P et al. 1998. HPV and intraepithelial neoplasia recurrent lesions of the lower genital tract: Assessment of the immune system. Eur J Gynaecol Oncol 19(5): 466–469.
Stewart AC et al. 1996. Intratype variation in 12 human papillomavirus types: A worldwide perspective. J Virol 70(5): 3127–3136.
Terai M et al. 1999. High prevalence of human papillomavirus in the normal oral cavity of adults. Oral Mircobiol Immunol Aug 14(4): 201–205.
Walboomers JM et al. 1999. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189(1): 12–19.
Wen LM et al. 1999. Risk factors for the acquisition of genital warts: Are condoms protective? Sex Transm Infect 75: 312–316.
Ylitalo N et al. 1999. Smoking and oral contraceptives as a risk factors for cervical intraepithelial neoplasia. Int J Cancer 81(3): 357–365.
JHPIEGO, an affiliate of Johns Hopkins University, is a nonprofit corporation dedicated to improving the health of women and families throughout the world. JHPIEGO works to increase the number of qualified health professionals trained in modern reproductive healthcare, especially family planning.
JHPIEGO Corporation
Brown’s Wharf • 1615 Thames Street, Suite 200 • Baltimore, Maryland 21231-3492 • USA
http://www.jhpiego.orgCopyright© 2000 by JHPIEGO Corporation. All rights reserved.
Funding provided by the Bill and Melinda Gates Foundation through the Alliance for Cervical Cancer Prevention; and the United States Agency for International Development (USAID) Office of Population, Center for Population, Health and Nutrition/Global Programs, Field Support and Research Bureau/CMT Division, under the terms of Award No. HRN-A-00-98-00041-00. The opinions expressed herein are those of JHPIEGO and do not necessarily reflect the views of the Gates Foundation or USAID.
Printed in the United States of America