Human Papilloma Virus Vaccine

human papilloma virus vaccine

Abstract

Identifying human papilloma viruses related to the pathogenesis of cancer cervix and producing vaccines against them offered hopes for primary prevention of cancer cervix. Understanding the virus and the natural history of HPV infection recommends the use of the vaccine. However; debates on the compulsory use of the vaccine for young age females delays the legislations needed. The aim of this essay is to review, briefly, HPV vaccination and spotlight the debate about how important it is as a preventive measure against cancer cervix.

Introduction

In 1842, Rigoni Stern presented his observation that nuns never get cervical cancer to the 4^th Congress of Italian Scientists. This pointed out the possibility that sexually transmitted infection may be the cause of cervical cancer (Harper, 2004). Since then, many types of human papilloma virus (HPV) were identified to cause certain human diseases. The most serious health problem with HPV is that it is an important causative agent for cancer cervix (types 6, 11, 16, 18) (Bishop and others, 2007). Virus transmission occurs through sexual contact and infection may give no symptoms (silent infection). HPV infection is the commonest sexually transmitted infection in the US, by the age of 50, 80% of women in the US have had the chance to catch infection (National Cancer Institute 2006). I support giving HPV vaccine to females between the ages of 9 to 26 because of the possible serious outcome of HPV infection; as recommended by the Advisory Committee on Immunization Practices (ACIP) on June 2006 (ACIP 2006). Therefore; my essay is directed to parents and young sexually active females to spotlight how serious the consequences of human papilloma virus infection can be and how important is their support to HPV vaccination.

Background

Papilloma virus is a double strand circular DNA virus. The epithelial cells in certain tissues as the skin and the ano-genital tract are the target cells of infection are. Papilloma virus capsids (outside capsule like envelop around the virus DNA) contain two characteristic proteins (virally encoded proteins) called L1 and L2. These virally encoded proteins develop late in the infection cycle. These capsids are made of protein with L1 proteins having the intrinsic ability of self-assembly forming virus like particles (VLP) which are, in fact, empty capsids. The use of VLPs as a vaccine is because they are similar, immunologically, to the infecting virus (Bishop and others 2007).

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The question now is what happens when HPV infection occurs? The natural course (sequence of events) of infection takes three forms (Harper 2004). The first form is episomal infection (virus-latency or latent period of HPV infection). The virions (small virus particles) transmitted from one epithelial surface (superficial cells) become attached to another epithelial surface. Virions, then, find its way to the deeper (basal) cells. Characteristic to this stage is the association with low virus copy numbers and that is the reason for missing HPV in routine histo-pathological scrapping examination. The second form is when the virus genome (DNA) copies itself faster than the host cell DNA. In this stage, the epithelium may show some metaplasia (cell character or order change). The third form occurs when high risk virus genome incorporates with basal cell DNA with the release of precancerous substances (CIN) (Harper 2004).

Cervical cancer is the third cancer that affects the female genital tract in the US (after cancer ovary and carcinoma of the uterine endometrium). It is the eighth cancer if we look to all body organs. The incidence of cervical cancer shows ethnic variations, in American white females, the incidence is 8.6 each 100.000. In African-American females, it incidence is 13 each 100.000. In Asian-American females, it is 9.3 by 100.000, while in Hispanic (Latino) females; the ratio is 14.7 each 100.000. The main reasons which predispose to cancer cervix are; practicing sexual activity at an early age, multiple sexual partners, persistent infection with papilloma virus and cigarette smoking. The major factor affecting prognosis is early detection since the 5 years survival rate is 48% when discovered in late stages. The 5 years survival rate of preinvasive (early) cases is near 100% (Benedet and others 2001).

A quadrivalent HPV vaccine (types 6, 11, 16, 18) developed, recently, and approved by the FDA (Food and Drug Administration) in June 2006. According to FDA report in 2006, it is a significant step forward to prevent female HPV infection which is an important reason for developing cancer cervix (FDA News 2006). The vaccine is prepared from virus like particles (VLP) which lack DNA and therefore non infective combined with an adjuvant. The dose of vaccine is three intramuscular 0.5 ml doses with intervals of two months after the first dose and six months after the second (Cutts and others 2007). The vaccine is recommended for females nine to 26 years old. Females of young age are vaccinated because it is important to give them the vaccine before sexual activity. Parent should be acknowledged that the vaccine is only prophylactic and will not prevent the disease caused by any type of HPV if infection with that type has already occurred. Pregnant females are discouraged of taking the vaccine as its impact on the unborn fetus needs further studies. Any female who is mildly ill can still get the vaccine, but those who are moderately or severely ill should postpone the dose till they recover. Finally, those with known history of allergy to yeast (adjuvant) or to a previous dose of the vaccine should get the vaccine or following doses (ACIP 2006).

Discussion

Cons: The debate against HPV vaccine is on four main issues. First, knowing that health care authorities encourage HPV; should legislations be made to make the vaccine a school mandate? HPV is not a causal or droplet infection such as measles or pertussis. It needs practices that are not usual at schools at such a young age. Therefore; there is no immediate need to give the vaccine as a preschool requirement. The right of parents to refuse vaccinating their daughters is the second issue. Third, is cost-effectiveness, as the price of the three doses is 360 US$, this raises the question of funding compulsory schoolgirls vaccination. Finally, as there is no vaccine that is safe or effective, should not we wait for further confirming studies (Weber 2007)?

HPV vaccine side effects range from mild to severe. Mild side effects include: pain at the site of injection (80%), redness or swelling at the site of injection (25%), mild fever (10%) and itching at the injection site (3.3%). Moderate fever i.e. 102 F occurs in 1 female vaccinated by 65. Severe risk may develop because of severe allergic reactions (ACIP 2006). However; HPV vaccine does not have a therapeutic effect on a female that have the virus nor can it prevent the disease caused by that virus (ACIP 2006).

The routine screening using Papinicolaou (pap) test to detect cervical precancer lesions succeeded in reducing the overall decrease in cervical cancer incidence by 70% over the last 50 years (Guido 2004). Dungan, 2007, argues that it is better to educate women on safe sex and abstinence. Yearly pap test should not be discouraged. It might be better to improve these two lines than to provide a vaccine without being aware its long-term effects or for how long does it provide protection against the virus.

Pros: Epidemiological studies show that nearly 20 million men and women are infected with HPV in the US. Additionally about 6.2 million get infected each year, and 50% of sexually active men and women are HPV infected. Although HPV infection may cause no symptoms, yet infection is important for developing cancer cervix. Cancer cervix affect 10000 women in the US every year of them 3700 die of it (ACIP 2006).

HPV vaccine is effective against two viruses blamed for about 70% of cases showing malignant transformation of cells (type 16, 18) and two more viruses that cause about 90% of benign genital warts (CIAP 2006). The vaccine is made of VLPs devoid of DNA and thus is not capable of producing a disease. The vaccine does not cause serious or life threatening side effects (CIAP 2006). In addition, the vaccine is expected to give long term immunity (good immune memory) and therefore, it is likely to provide long-term protection (Stanley 2007).

The vaccine is expensive, yet the cost of treatment of cancer cervix is much higher. Studies showed that if the vaccine is effective against HPV type 16, 18 only, being immune saves 15.000 to 25000 US$. In addition, the US Health Department provides vaccination at minimum or no charge for those who cannot afford it (ACIP 2006).

The prospects of HPV vaccination are notable. FDA approved the vaccine (FDA 2006) and both the Advisory Committee on Immunization Practices (ACIP 2006) and the National Cancer Institute (2006) advise giving it to females between 9 to 26 years old. For a successful introduction of the vaccine, nationwide, there is the need for support of policy decision makers', healthcare professionals and the public specially parents and sexually active females. Therefore; essential communication strategies are essential for a successful HPV vaccine program.

Conclusion

Human papilloma virus vaccine contributes to improving the incidence of cervical cancer. Sex education and regular screening have proved relatively effective in preventing cancer cervix. However, complying of all sexually active females to these measures is questionable. A decision of approving HPV vaccine is a decision of saving lives. For better efficacy, the vaccine has to be given before the age of sexual activity. Therefore; filling the communication gap with parents is important. Making it mandatory needs state legislations which in turn need discussion with healthcare workers to solve the issues delaying legislations making the vaccine affordable to anyone irrespective of their social or economic status.

References

Harper, D.M (2004). Why am I scared of HPV (Editorial). CA Cancer J Clin, 54, 245-247.

Bishop, B, Dasgupta, J, Klein, M, Garcea, R.L et al (2007). Crystal Structures of four types of human papilloma virus L1 capsid proteins. J. Biol. Chem., 43, 31803-31811.

National Cancer Institute (2006). HPV- Vaccine: Question and answers for the public. Retrieved 02/07/2008, from <http://www.cdc.gov/vaccines/vpd-vac/hpv/hpv-vacsafe-effic.htm>

Advisory Committee on Immunization Practices (ACIP) (2006).HPV (human papilloma virus) vaccine: What you need to know. Retrieved 02/07/2008, from <http://www.cdc.gov/vaccines/recs/acip>

Howe, H.L, Wu, X., Ries, L.A et al (2006). Annual report to the nation on the status of cancer 1975-2003 featuring cancer among US Hispanic/Latino populations. Cancer, 107, 1643-1658.

Benedet, J.L, Odicino, F, Maisonneuve, P et al (2001). Carcinoma of the cervix uteri. J Epidemiol Biostat, 6 (1), 7-43.

FDA News (June 8, 2006). FDA Licenses New Vaccine for Prevention of Cervical Cancer and Other Diseases in females caused by human papilloma virus. US Food and Drug Administration, News. Retrieved 02/07/2008, from <http://www.fda.gov>.

Cutts, F.T, Franceschi, S, Goldie, X et al (2007). Human papilloma virus and HPV vaccines: a review. Bulletin of the World Health Organization, 85, 719-726.

Weber, C.J (2007). Update on vaccination against human papilloma virus (HPV). Urologic Nursing, 27 (4), 320-321.

Guido, R (2004). Guidelines for screening and treatment of cervical disease in the adolescent. J pediatr Adolesc Gynaecol, 17, 303-311.

Dungan, D (2007). Pros and cons of HPV vaccine debate: Gardasil remains controversial despite FDA approval. Idaho Mountain Express. Retrieved 02/07/2008 from <http://www.mtexpress.com/index2.php?ID=2005113740>

Stanley, M (2007). Prophylactic HPV vaccines. Journal of Clinical Pathology, 60, 961-965.