HOW TO AVOID CERVICAL CANCER

Rebecca B. Singson, M.D., FPOGS

Globally, one woman dies of cervical cancer every 2 minutes, and some 500 thousand new cases of this disease are seen every year. Cervical cancer is the 2^nd most common cancer in women second only to breast cancer, afflicting 7225 new cases in in the Philippines according to our National Cancer Institute 2005 statistics. However, cervical cancer is a more deadly disease because for every 4 Filipino women who survive cancer of the breast, only 2 or 3 will survive cancer of the cervix.

Using a protocol assembled by the International Agency for Research on Cancer (IARC) from biopsy specimens from 22 countries, it was shown that the Human Papillomavirus (HPV) was present and is a necessary cause of cervical cancer (2,3) There are also other cancers to which the HPV has been linked to such as cancers of the vulva and the anus and penis. They start off as warts which eventually become tumorous growths. Increasing evidence has also been linking HPV as an important carcinogenic agen in cancers of the oral cavity, pharynx and larynx. 4.

HOW DO YOU GET IT?

The virus is acquired sexually and it seems the younger a woman starts sexual intercourse (especially

WHO ARE AT HIGH RISK?

HOW IS IT PREVENTED?

1, Male circumcision. The IARC multicentric study on maile cicrumscion revealed that circumcised men were about 3 times less likely to harbor HPV in their male organ than uncircumcised males.

The Young Adult Fertility Study (YAFS) 2002 revealed that 1.2% of our youth will have had their 1^st sexual contact before 13 yrs old, the youngest reported was at 8 years old. Twelve percent of the females while 28% of the males would have started sexual contact before 18. In fact, 38% of our youth are already in a live-in arrangement. These statistics are disturbing. If these youth knew that early sex and early pregnancy and multiple sexual partners increased their risk for acquiring the virus that causes cervical cancer, would they be empowered to make more intelligent choices?

During the recent Asia Oceania (research organization on) Genital Infection & Neoplasia (AOGIN), world experts on the Human Papilloma Virus and cervical cancer gathered from 18 countries to discuss global initiatives on cervical cancer prevention.

In Asia, there are 266,000 new cases of cervical cancer diagnosed each year. In 2005, alone our National Cancer Institute statistics reveals that there are 7225 new cases of cervical cancer in the Philippines. The sad thing is that two-thirds of these cases are diagnosed at a late stage when they are beyond the operative stage. So it is not surprising that 32.3% of them die in 1 year and 73% will die in 5 years. The sad part is that it is completely preventable, or at least diagnosable before it becomes life threatening.

WHAT CAUSES CERVICAL CANCER?

In the past 2 decades, substantial progress in our understanding of the natural history of cervical cancer have led us to conclude that a virus called the Human papillomavirus (HPV) is now recognized as the main cause of cervical cancer. ¹ There are more than 70 distinct site-specific types (meaning they will grow on one part of the body but not on another). Of these, about 35 types are found in the anus and the genital areas, causing warts and cervical cancer, the most notorious being types 16 and 18. It is a virus acquired through sexual contact and infects the lining cells of the genitalia and can be detected in 5%-40% of women of reproductive age.² It has been found that infections are relatively short-lived lasting usually 8-10 months.³ This indicates that our bodies are indeed capable of clearing the virus which is why in women over 30 years old, the prevalence drops down to 5-10%. Persistent infections, however, are found in 5-10% in women over 35 years old.⁴ It is in this group of women who are not able to clear the virus from their bodies that cancer in the cervix now has a chance to progress. The virus is apparently able to thrive in the cells without killing it and without inducing any immunologic reaction from the patient. The body therefore “ignores” the virus allowing it to eventually alter the genetic code of the cells. As a result, the cervix starts multiplying cells which become cancerous after many years.

FACTORS THAT INCREASE ONE’S RISK FOR CERVICAL CANCER

It is important to understand the risk factors that increase your chances of acquiring the virus as well as the co-existing factors that mediate progression to cancer. In a case-control study of women with invasive cervical cancer in four Latin American countries where they evaluated cervical cancer risk in relation to sexual behavior, histories of specific venereal diseases, and hygiene practices, it was noted that early age at first sexual intercourse and increasing number of sexual partners were associated with significantly increased risk for cervical cancer. Risk increased over twofold among women reporting first intercourse at 14 to 15 years of age compared with those who started after 20 years old.⁵ An initial pregnancy before 18 yrs. old and multiple pregnancies (over 5) as well as a history of having acquired a sexually transmitted disease (STD) also increase your risk. Having an uncircumcised male partner, cigarette smoking, an impaired immune system (such as AIDS patients), and poor nutrition (diet low on fruits & vegetables and deficient in Vit A, C & folic acid) all increase ones’s risk for cervical cancer. ⁶

SEXUAL PRACTICES OF THE YOUTH IN THE PHILIPPINES

WHAT TO DO

It is vital for us to educate our youth that it is prudent for men as well as women to delay having sex as late as possible. This is because the earlier you engage in sexual intercourse, the higher the chances for having multibple sexual partners which will increase the chances of acquiring the carcinogenic Human Papillomavirus. Men should realize that although the virus does not cause much harm to them in general other than occasionally causing unsightly penile warts, through their sexual practices, they can transmit the virus to their unsuspecting, innocent monogamous sexual partners. Engaging in sex early has also been linked to increased number of early, unwanted pregnancies which can also increase chance for the virus to mutate the genetic code (because of the immunocompromised state during pregnancy) of the cell to promote cervical cancer. The youth must know that promiscuity can be potentially lethal if one acquires the HPV virus or worse, AIDS so sex should be limited to a significant other or to one destined to be a lifetime partner. It might help them to know that choosing a circumcised male partner can also decrease one’s risk for cervical cancer.

Once the females start becoming sexually active, she should start seeing a gynecologist. Within 3 years from her first sexual contact, she should start getting Pap smears, which has been the most widely used screening test for cervical cancer. Unfortunately, there are many pitfalls to this since nearly half of specimens miss a cancer in the reading; about one-third of these false-negative readings are attributable to errors in interpreting slides and two-thirds to poor sample collection and slide preparation.⁷

However, a test already exists to detect the presence of the virus which uses a method similar to the Pap smear using a different cervical brush. It is currently available at the Makati Medical Center, the Asian Hospital & Medical Center, Medical City, St Luke’s and one center in Cebu. Made by the Digene Co, the Human Papillomaviurs test may be recommended to all women over 30 years and above together with a Pap smear. If both tests trun up negative, and the last three Pap smears were normal, you can even defer you next Pap smear test for 3 years because in the absence of the virus, is unlikely that you will develop cervical cancer in 3 years. If your test turns up positive, you may either opt for a repeat testing in 1 year or colposcopy of the cervix to check for possible.precancerous changes.

FUTURE THRUSTS

The era has arrived where two major pharmaceuticals (GSK and Merck) are already doing human trials on an HPV vaccines in the hope of reducing the risk for cervical cancer. Hopefully in 2 years, at least one of them will receive FDA approval from the U.S and be commercially available. It is hoped that such vaccines would boost an immune response against the development of cancer or even existing tumors. Preliminary trials of the vaccine have shown some promising success. Hopefully, mass vaccinations at around 10 years old before the woman becomes sexually active can someday help to eradicate a deadly cancer from the face of the earth.

1. Ladines-Llave , Cecilia, Burden of Cervical Cancer in the Philippines and Efforts to Combat the Disease (This paper was presented at the John Hopkins-JHPIEGO Global Conference on Low-Resource Setting Cervical Cancer Prevention, held in Bangkok, Thailand on Dec. 4, 2005)
2. Bosch FX, et al, The ABSCC study group. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst 1995; 87: 796-802.
3. Walboomers JM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999: 189:12-9.
4. .Munoz N, et al. Chapter 1: HPV in the etiology of human cancer. Vaccine 24S3 (2006) S3/1-3/10.

¹Jan M. M. Walboomers, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. The Journal of Pathology, 189: 1, 12-19.
² Franco EL, Villa LL, Richardson H, Rohan T, Ferenczy A. Epidemiology of cervical human papillomavirus infection. In: Franco EL, Monsonégo J, editors. New developments in cervical cancer screening and prevention. Oxford (UK): Blackwell Science; 1997. p. 14-22.
³Ho GYF, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998; 338: 423-28.
⁴Shah KV, Howley PM Papillomavirus. In: Fields MN, et al, ed. Fields Virology, 3rd edition, Philadelphia: Lippencott Raven, 1988:2077-2109.
⁵Herrero R, et al. Sexual behavior, venereal diseases, hygiene practices, and invasive cervical cancer in a high-risk population. Cancer. 1990 Jan 15;65(2):380-6.
⁶www.emoryhealthcare.org/HealthGate/32624.html

⁷McCrory DC, Matchar DB, Bastian L, Datta S, Hasselblad V, Hickey J, et al. Evaluation of cervical cytology. Evidence report/technology assessment no 5; AHCPR publ no 99-E010. Rockville (MD): Agency for Health Care Policy and Research; 1999.

SEXUAL PRACTICES THAT INCREASE YOUR RISK FOR CERVICAL CANCER

Rebecca B. Singson, M.D., FPOGS

During the recent Asia Oceania (research organization on) Genital Infection & Neoplasia (AOGIN), world experts on the Human Papilloma Virus and cervical cancer gathered from 18 countries to discuss global initiatives on cervical cancer prevention.

In Asia, there are 266,000 new cases of cervical cancer diagnosed each year. In 2005, alone our National Cancer Institute statistics reveals that there are 7225 new cases of cervical cancer in the Philippines. The sad thing is that two-thirds of these cases are diagnosed at a late stage when they are beyond the operative stage. So it is not surprising that 32.3% of them die in 1 year and 73% will die in 5 years. The sad part is that it is completely preventable, or at least diagnosable before it becomes life threatening.

WHAT CAUSES CERVICAL CANCER?

In the past 2 decades, substantial progress in our understanding of the natural history of cervical cancer have led us to conclude that a virus called the Human papillomavirus (HPV) is now recognized as the main cause of cervical cancer. ¹ There are more than 70 distinct site-specific types (meaning they will grow on one part of the body but not on another). Of these, about 35 types are found in the anus and the genital areas, causing warts and cervical cancer, the most notorious being types 16 and 18. It is a virus acquired through sexual contact and infects the lining cells of the genitalia and can be detected in 5%-40% of women of reproductive age.² It has been found that infections are relatively short-lived lasting usually 8-10 months.³ This indicates that our bodies are indeed capable of clearing the virus which is why in women over 30 years old, the prevalence drops down to 5-10%. Persistent infections, however, are found in 5-10% in women over 35 years old.⁴ It is in this group of women who are not able to clear the virus from their bodies that cancer in the cervix now has a chance to progress. The virus is apparently able to thrive in the cells without killing it and without inducing any immunologic reaction from the patient. The body therefore “ignores” the virus allowing it to eventually alter the genetic code of the cells. As a result, the cervix starts multiplying cells which become cancerous after many years.

FACTORS THAT INCREASE ONE’S RISK FOR CERVICAL CANCER

It is important to understand the risk factors that increase your chances of acquiring the virus as well as the co-existing factors that mediate progression to cancer. In a case-control study of women with invasive cervical cancer in four Latin American countries where they evaluated cervical cancer risk in relation to sexual behavior, histories of specific venereal diseases, and hygiene practices, it was noted that early age at first sexual intercourse and increasing number of sexual partners were associated with significantly increased risk for cervical cancer. Risk increased over twofold among women reporting first intercourse at 14 to 15 years of age compared with those who started after 20 years old.⁵ An initial pregnancy before 18 yrs. old and multiple pregnancies (over 5) as well as a history of having acquired a sexually transmitted disease (STD) also increase your risk. Having an uncircumcised male partner, cigarette smoking, an impaired immune system (such as AIDS patients), and poor nutrition (diet low on fruits & vegetables and deficient in Vit A, C & folic acid) all increase ones’s risk for cervical cancer. ⁶

SEXUAL PRACTICES OF THE YOUTH IN THE PHILIPPINES

In the Philippines, the YAFS study 2002 revealed that 1.2% of our youth will have had their 1^st sexual contact before 13 yrs old, the youngest reported was at 8 years old. Twelve percent of the females while 28% of the males would have started sexual contact before 18. In fact, 38% of our youth are already in a live-in arrangement. These statistics are disturbing. If these youth knew that early sex and early pregnancy and multiple sexual partners increased their risk for acquiring the virus that causes cervical cancer, would they be empowered to make more intelligent choices?

WHAT TO DO

It is vital for us to educate our youth that it is prudent for men as well as women to delay having sex as late as possible. This is because the earlier you engage in sexual intercourse, the higher the chances for having multibple sexual partners which will increase the chances of acquiring the carcinogenic Human Papillomavirus. Men should realize that although the virus does not cause much harm to them in general other than occasionally causing unsightly penile warts, through their sexual practices, they can transmit the virus to their unsuspecting, innocent monogamous sexual partners. Engaging in sex early has also been linked to increased number of early, unwanted pregnancies which can also increase chance for the virus to mutate the genetic code (because of the immunocompromised state during pregnancy) of the cell to promote cervical cancer. The youth must know that promiscuity can be potentially lethal if one acquires the HPV virus or worse, AIDS so sex should be limited to a significant other or to one destined to be a lifetime partner. It might help them to know that choosing a circumcised male partner can also decrease one’s risk for cervical cancer.

Once the females start becoming sexually active, she should start seeing a gynecologist. Within 3 years from her first sexual contact, she should start getting Pap smears, which has been the most widely used screening test for cervical cancer. Unfortunately, there are many pitfalls to this since nearly half of specimens miss a cancer in the reading; about one-third of these false-negative readings are attributable to errors in interpreting slides and two-thirds to poor sample collection and slide preparation.⁷

However, a test already exists to detect the presence of the virus which uses a method similar to the Pap smear using a different cervical brush. It is currently available at the Makati Medical Center, the Asian Hospital & Medical Center, Medical City, St Luke’s and one center in Cebu. Made by the Digene Co, the Human Papillomaviurs test may be recommended to all women over 30 years and above together with a Pap smear. If both tests trun up negative, and the last three Pap smears were normal, you can even defer you next Pap smear test for 3 years because in the absence of the virus, is unlikely that you will develop cervical cancer in 3 years. If your test turns up positive, you may either opt for a repeat testing in 1 year or colposcopy of the cervix to check for possible.precancerous changes.

FUTURE THRUSTS

The era has arrived where two major pharmaceuticals (GSK and Merck) are already doing human trials on an HPV vaccines in the hope of reducing the risk for cervical cancer. Hopefully in 2 years, at least one of them will receive FDA approval from the U.S and be commercially available. It is hoped that such vaccines would boost an immune response against the development of cancer or even existing tumors. Preliminary trials of the vaccine have shown some promising success. Hopefully, mass vaccinations at around 10 years old before the woman becomes sexually active can someday help to eradicate a deadly cancer from the face of the earth.

¹Jan M. M. Walboomers, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. The Journal of Pathology, 189: 1, 12-19.
² Franco EL, Villa LL, Richardson H, Rohan T, Ferenczy A. Epidemiology of cervical human papillomavirus infection. In: Franco EL, Monsonégo J, editors. New developments in cervical cancer screening and prevention. Oxford (UK): Blackwell Science; 1997. p. 14-22.
³Ho GYF, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998; 338: 423-28.
⁴Shah KV, Howley PM Papillomavirus. In: Fields MN, et al, ed. Fields Virology, 3rd edition, Philadelphia: Lippencott Raven, 1988:2077-2109.
⁵Herrero R, et al. Sexual behavior, venereal diseases, hygiene practices, and invasive cervical cancer in a high-risk population. Cancer. 1990 Jan 15;65(2):380-6.
⁶www.emoryhealthcare.org/HealthGate/32624.html
⁷McCrory DC, Matchar DB, Bastian L, Datta S, Hasselblad V, Hickey J, et al. Evaluation of cervical cytology. Evidence report/technology assessment no 5; AHCPR publ no 99-E010. Rockville (MD): Agency for Health Care Policy and Research; 1999.

PREVENTING CERVICAL CANCER THROUGH YOUR SEXUAL HABITS

Rebecca B. Singson, M.D., FPOGS

Over a century ago, it was observed that women who developed cervical cancer were among those with husbands who traveled frequently, or who had penile cancer, or whose wife had died of cervical cancer, or those who fleeted from one sexual partner to another. It was not until the past 2 decades that research has shown that one of the main causes of cervical cancer is a virus called the Human Papillomavirus.¹

Cervical cancer is the most common cancer in the female reproductive tract and is the second most common cancer in women next to breast cancer. In Asia, there are 266,000 new cases of cervical cancer diagnosed each year. In 2005, alone our National Cancer Institute statistics reveals that there are 7225 new cases of cervical cancer in the Philippines. The sad thing is that two-thirds of these cases are diagnosed at a late stage when they are beyond the operative stage. So it is not surprising that 32.3% of them die in 1 year and 73% will die in 5 years. The irony is that it is completely preventable, or at least diagnosable before it becomes life threatening.

During the recent Asia Oceania (research organization on) Genital Infection & Neoplasia (AOGIN), world experts on the Human Papilloma Virus and cervical cancer gathered from 18 countries to discuss global initiatives on cervical cancer prevention.

WHAT DO WE KNOW ABOUT THIS VIRUS?

World experts on the Human Papillomavirus from 18 countries gathered recently to organize the Asia Oceania (research organization on) Genital Infection & Neoplasia (AOGIN) to share with each other their latest research on the virus and to discuss global intitiatives on cervical cancer prevention. It was revealed that there are more than 70 distinct site-specific types (meaning they will grow on one part of the body but not on another) of this virus. Of these, about 35 types are found in the anus and the genital areas, causing warts and cervical cancer, the most notorious being types 16 and 18. It is a virus acquired through sexual contact and infects the lining cells of the genitalia and can be detected in 5%-40% of women of reproductive age.² It has been found that infections are relatively short-lived lasting usually 8-10 months.³ This indicates that our bodies are indeed capable of clearing the virus which is why in women over 30 years old, the prevalence drops down to 5-10%. Persistent infections, however, are found in 5-10% in women over 35 years old.⁴ It is in this group of women who are not able to clear the virus from their bodies that cancer in the cervix now has a chance to progress. The virus is apparently able to thrive in the cells without killing it and without inducing any immunologic reaction from the patient. The body therefore “ignores” the virus allowing it to eventually alter the genetic code of the cells. As a result, the cervix starts multiplying cells which become cancerous after many years.

FACTORS THAT INCREASE ONE’S RISK FOR CERVICAL CANCER

It is important to understand the risk factors that increase your chances of acquiring the virus as well as the co-exisiting factors that mediate progression to cancer. In a case-control study of women with invasive cervical cancer in four Latin American countries where they evaluated cervical cancer risk in relation to sexual behavior, histories of specific venereal diseases, and hygiene practices, it was noted that early age at first sexual intercourse and increasing number of sexual partners were associated with significantly increased risk for cervical cancer. Risk increased over twofold among women reporting first intercourse at 14 to 15 years of age compared with those who started after 20 years old.⁵ An initial pregnancy before 18 yrs. old and multiple pregnancies (over 5) as well as a history of having acquired a sexually transmitted disease (STD) also increase your risk. Having an uncircumcised male partner, cigarette smoking, an impaired immune system (such as AIDS patients), and poor nutrition (diet low on fruits & vegetables and deficient in Vit A, C & folic acid) all increase ones’s risk for cervical cancer. ⁶

SEXUAL PRACTICES OF THE YOUTH IN THE PHILIPPINES

In the Philippines, the YAFS study 2002 revealed that 1.2% of our youth will have had their 1^st sexual contact before 13 yrs old, the youngest reported was at 8 years old. Twelve percent of the females while 28% of the males would have started sexual contact before 18. In fact, 38% of our youth are already in a live-in arrangement. These statistics are disturbing because the youth are engaging in practices that increase their exposure to acquiring the virus that causes cervical cancer.

Is There a Way to Test if You are Positive for the Human Papillomavirus?

Because of advances in our knowledge linking the human papillomavirus to the causation of cervical cancer, it became necessary to develop HPV tests that would indicate if the woman was positive for the high-risk strains of the virus that would increase her risk for cervical cancer. The HPV DNA test using the Hybrid Capture II System, developed by a company called DIGENE, recently came out with a commercially available test which has a sensitivity of >90%1 and a negative predictive value of over 90%8. Available in major hospitals, the test entails taking cervical swabs, much like a Pap smear, using the

brush from the Digene Cervical Sampler. Pap smear collected with a broom collection device and rinsed in the ThinPrep System PreservCyt@ solution may also be used to provide the same specimen for HPV testing. (You see, Pap smears are done in 2 ways: the conventional way is by smearing the cervical swab on a glass slide; the latest way is to use the broom collection device with the ThinPrep System. The latter has the advantage of providing the sample to test for HPV testing in case you deem it necessary. So, you can in fact ask your gynecologist to perform the test when you get your next Pap smear. There have even been been studies in China and in Canada where the women performed the swabs on themselves by inserting the cervical brush intravaginally, trying to reach the cervix, referred to as self-collection which also yielded satisfactory results .

Many recent studies have shown that the combination of HPV DNA test and Pap smear improves the detection rate of pre-cancerous lesions of the cervix compared to Pap smear alone.^8-10

WHAT TO DO

It is vital for us to educate our youth that it is prudent for men as well as women to delay having sex as late as possible. This is because the earlier you engage in sexual intercourse, the higher the chances for having multiple sexual partners which will increase the chances of acquiring the carcinogenic Human Papillomavirus. Men should realize that although the virus does not cause much harm to them in general other than occasionally causing unsightly penile warts, through their sexual practices, they can transmit the virus to their unsuspecting, innocent monogamous sexual partners. Engaging in sex early has also been linked to increased number of early, unwanted pregnancies which can also increase chance for the virus to mutate the genetic code (because of the immunocompromised state during pregnancy) of the cell to promote cervical cancer. The youth must know that promiscuity can be potentially lethal if one acquires the HPV virus or worse, AIDS so sex should be limited to a significant other or to one destined to be a lifetime partner. It might help them to know that choosing a circumcised male partner can also decrease one’s risk for cervical cancer.

Once the females start becoming sexually active, she should start seeing a gynecologist. Within 3 years from her first sexual contact, she should start getting Pap smears, which has been the most widely used screening test for cervical cancer. Unfortunately, there are many pitfalls to this since nearly half of specimens miss a cancer in the reading; about one-third of these false-negative readings are attributable to errors in interpreting slides and two-thirds to poor sample collection and slide preparation.¹¹

The Human Papillomaviurs test may be recommended to all women over 30 years and above together with a Pap smear. If both tests run up negative, and the last three Pap smears were normal, you can even defer you next Pap smear test for 3 years because in the absence of the virus, it is unlikely that you will develop cervical cancer in 3 years. If your test turns up positive, you may either opt for a repeat testing in 1 year or go for colposcopy of the cervix to check for possible precancerous changes.

FUTURE THRUSTS

The era has arrived where two major pharmaceuticals (GSK and Merck) are already doing human trials on an HPV vaccines in the hope of reducing the risk for cervical cancer. Hopefully in 2 years, at least one of them will receive FDA approval from the U.S and be commercially available. It is hoped that such vaccines would boost an immune response against the development of cancer or even existing tumors. Preliminary trials of the vaccine have shown some promising success. Hopefully, mass vaccinations at around 10 years old before the woman becomes sexually active can someday help to eradicate a deadly cancer from the face of the earth.

¹Jan M. M. Walboomers, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. The Journal of Pathology, 189: 1, 12-19.
² Franco EL, Villa LL, Richardson H, Rohan T, Ferenczy A. Epidemiology of cervical human papillomavirus infection. In: Franco EL, Monsonégo J, editors. New developments in cervical cancer screening and prevention. Oxford (UK): Blackwell Science; 1997. p. 14-22.
³Ho GYF, et al. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998; 338: 423-28.
⁴Shah KV, Howley PM Papillomavirus. In: Fields MN, et al, ed. Fields Virology, 3rd edition, Philadelphia: Lippencott Raven, 1988:2077-2109.
⁵Herrero R, et al. Sexual behavior, venereal diseases, hygiene practices, and invasive cervical cancer in a high-risk population. Cancer. 1990 Jan 15;65(2):380-6.
⁶www.emoryhealthcare.org/HealthGate/32624.html
⁷ “Youth, Sex and Risk Behaviors in the Philippines” published by the Demographic Research and Development Foundation (DRDF). For more information, contact Dr. Corazon M. Raymundo, Project Overall Coordinator, YAFS3; e-mail: craymund@psdn.org.ph
⁸ Ferenczy A, et al. Diagnostic performance of Hybrid Capture human papillomavirus deoxyiribonucleic acid combined with liquid-based cytologic study. Am J Obstet Gynecol. 1966; 175: 651-656.
⁹ Manos MM, et al. Identifying women with cervical neoplasia using himan papillomavirusDNA testing for equivocal Papanicolau results.JAMA 1999;281:1605-1610.
¹¹ WrightTC, et al. Comparison of management algorithms for the evaluation of women with low-grade cytologic abnormalities. Obstet Gynecol 1995, 85:202-210.

THE HUMAN PAPILLOMAVIRUS & THE CERVICAL CANCER CONNECTION

REBECCA B. SINGSON, M.D., F.P.O.G.S.

Cervical cancer is the most common cancer in the female reproductive

system. It is the second most common cancer afflicting females second only

to breast cancer. What most people don't realize is that cervical cancer

is now recognized to be the first identified virally induced cancer in

women.1 Research over the last few years has provided overwhelming

evidence that infections with a high risk type of cancer-inducing Human

papillomavirus (HPV) is necessary for the development of cancer.2

Understanding what can cause it and knowing how to monitor cervical cancer

progression makes it one of the most highly preventable cancers afflicting

the female.

Was the Pap Smear Not Doing the Job?

There is no doubt that the introduction of cervical cytology introduced by

Papanicolau (thus called the Pap smear), had a major impact in bringing

about a significant reduction in the incidence of and mortality resulting

from cervical cancer in many countries.3 Applying this massive screening

program some fifty years ago has resulted in a 50-70% reduction of

mortality resulting from cervical cancer. However, even in highly

developed countries, this impact has not reached the desired levels

expected from implementing a massive screening program because it has not

resulted in the eradication of the disease and women are still dying from

it.4

A recent critical review of evidence-based data showed that a single Pap

smear misses up to 50% of cervical cancer precursor lesions.5 That's one

out of two!! Knowing this makes us now partly understand why cervical

cancer continues to occur at such unacceptably high incidence rates, even

in countries where the government spends money to subject its population

to massive screening.

Understanding What Causes Cervical Cancer: the Viral Connection

Although the sensitivity of the Pap smear in picking up cervical cancer

has not changed much in the last 10 years, there has been rapid growth in

our knowledge as to what causes cervical cancer. Research has shown that

the human papillomavirus is present in 99.7% of cervical cancers.2

What is this Wart-Causing Human Papillomavirus?

The human papillomavirus (HPV) is a double stranded DNA virus which

infects the surface cells lining our tissues called epithelial cells.

There are more than 70 distinct site-specific types (meaning they will

grow on one part of the body but not on another). Of these, about 35 types

are found in the anus and the genital areas, causing warts and cervical

cancer, the most notorious being types 16 and 18.

These infections are considered sexually transmitted and are among the

most common sexually transmitted diseases in most countries affecting up

to 40% of women with a yearly incidence of 10-15%6 . Many of the HPV

infections do not show any signs of symptoms, and are therefore

subclinical. It has been found that infections are relatively short-lived

lasting usually 8-10 months.7 This indicates that our bodies are indeed

capable of clearing the virus which is why in women over 30 years old, the

prevalence drops down to 5-10%. Persistent infections, however, are found

in 5-10% in women over 35 years old.6 It is in this group of women who are

not able to clear the virus from their bodies that cancer in the cervix

now has a chance to progress. Research in the last 10 years has consistently detected HPV in more than 90% of cases of cervical cancer, and in some studies, have found

it in all cases.1

Is There a Way to Test if You are Positive for the Human Papillomavirus?

Because of advances in our knowledge linking the human papillomavirus to

the causation of cervical cancer, it became necessary to develop HPV tests

that would indicate if the woman was positive for the high-risk strains of

the virus that would increase her risk for cervical cancer. The HPV DNA

test using the Hybrid Capture II System, developed by a company called

DIGENE, recently came out with a commercially available test which has a

sensitivity of >90%1 and a negative predictive value of over 90%8.

The test entails taking cervical swabs, much like a Pap smear, using the

brush from the Digene Cervical Sampler. Pap smear collected with a broom

collection device and rinsed in the ThinPrep System PreservCyt@ solution

may also be used to provide the same specimen for HPV testing. (You see,

Pap smears are done in 2 ways: the conventional way is by smearing the

cervical swab on a glass slide; the latest way is to use the broom

collection device with the ThinPrep System. The latter has the advantage

of providing the sample to test for HPV testing in case you deem it

necessary. So, you can in fact ask your gynecologist to perform the test

when you get your next Pap smear. There have even been been studies in

China and in Canada where the women performed the swabs on themselves by

inserting the cervical brush intravaginally, trying to reach the cervix,

referred to as self-collection which also yielded satisfactory results The

Digene HPV DNA test is the only FDA-approved test for detecting HPV.

Many recent studies have shown that the combination of HPV DNA test and

Pap smear improves the detection rate of pre-cancerous lesions of the

cervix compared to Pap smear alone.8-10

Is This Test Available in the Philippines?

Fortunately, yes. At the Makati Medical Center (MMC) and very soon, at the

Colposcopy Unit of the Asian Hospital and Medical Center. Hospitals from

all over the country can send their specimens to the MMC for testing. The

test costs 2,900 PHP and the results come out after two weeks since all

specimens are batched and ran once every two weeks for cost-effectivity.

What Does a Positive HPV Result Mean?

In women over 30, a positive result for high-risk types of HPVDNA means

that she has a potentially persistent infection which means that she has a

high risk of developing invasive cervical cancer. She should be

immediately referred for colposcopy. This procedure involves looking at

the cervix under high magnification, applying dyes to visualize abnormal

cervical tissue and performing a biopsy, when necessary, of these abnormal

areas. Women over 30 years old with a normal Pap smear but test positive

for high-risk HPV have a 116-fold risk for developing high grade

pre-cancerous lesions of the cervix compared to women who are

HPV-negative.

Women in their 20s with a positive HPV DNA result should have a repeat HPV

test after 9 months to one year. Since most HPV infections are transient,

the virus should normally be cleared in 9 months, particularly in women

younger than 30. If the test turns up to be negative, it means the

infection has resolved and the woman can be monitored subsequently with

Pap smears.

Are There Women Who Are At Increased Risk Than Others?

Since the virus is considered a sexually-transmitted disease, women who

started having contact at an age earlier than 18 are at greater risk of

acquiring the virus. Women who also have had more than 5 sexual partners

or have had partners who have had more than 5 sexual partners are also at

increased risk of being HPV positive.

It has been found that women who have had 5 vaginal births or more or have

had a pregnancy before 18 yrs. are at increased risk of developing

cervical cancer. It is possible that the immune state during pregnancy

allows the virus to exert changes in the DNA of the cervical cells, thus,

promoting cancer. It has also been found that smoking increases the risk

of cervical cancer as well as having a partner who is not

circumcised.

If any of the above conditions apply to you, it is best to test for HPV

DNA in order to know your risk for developing precursor lesions in the

cervix.

Our knowledge of cervical cancer has allowed man to create diagnostic

tests that can determine a woman's risk for developing cervical cancer. We

are at an era where cervical cancer is a highly preventable disease. To

die from it because we missed the test would be a crying shame.

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REFERENCES:

1 National Institutes of Health (NIH) Consensus Development Statement1996.
2 Walboomers JMMM, et al. Human papillomavirus, a necessary cause of invasive cervical cancer Worldwide. J Pathol.189:12-19 (1999).
3 Hakama M, et al. Effect of organized screening on the risk of cervical cancer in the Nordic countries. In Miller AB, et al (eds.): Cancer Screening. Cambridge, Cambridge University Press, 1991: 153-162.
4 Koss LG. The Papanicolau test for cervical cancerT detection: a triumphand a tragedy. JAMA1989; 261:737-43.
5 Federal study shows conventional Pap test remains most effective was to diagnose cervical cancer. ACOG Today, March 1999, 43 (3).
6 Shah KV, Howley PM Papillomavirus. In: Fields MN, et al, ed. Fields Virology, 3rd edition, Philadelphia: Lippencott Raven, 1988:2077-2109.
7 Ho GYF, et al. Natural history of cervicovaginal papillomavirusinfection in young women. N Engl J Med 1998; 338: 423-28.