Prevention Of Cervical Cancer Biology Essay


In Malaysia, cervical cancer is the 2nd most common cancer among women, amounting for 12.9 of all female cancer.3 Worldwide, there are 470,000 new cases of cervical cancer annually with deaths amounting to 233,000 people as reported by the U.S. Food and Drug Administration (FDA).24 Mortality rate of cervical cancer was 55%.

Cervical cancer (carcinoma of the uterine cervix) is a type of cancer affecting the cervix. Cancer is a disease in which abnormal cells multiply without control, destroying healthy tissue and endangering life.1 Almost all cervical cancer cases are associated with infection with the human papillomavirus (HPV).

Diagram 1: Location of the Cervix


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Cervical cancer begins with pre-cancer changes called cervical intraepithelial neoplasia (CIN). CIN progresses from mild to moderate to severe disease then invasive cancer over 7 to 20 years, usually with no symptoms. 16 Fortunately, cervical cancer is one of the easiest cancers to prevent and highly curable if detected early.

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Diagram 2: Progression of Cervical Cancer


Cervical cancer incidence and mortality is significantly higher in developing regions compared to developed regions as seen in Diagram 3. Thus cervical cancer is an important public health problem, especially affecting socioeconomically disadvantaged women in low-resource countries. 7

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Diagram 3: Cervical Cancer Burden Worldwide


Worldwide, one in ten female cancer deaths is due to cervical cancer. 22 Due to the prevalence of the HPV virus and the life-threatening dangers of cervical cancer, it is my opinion that prevention is always better than cure. If we could protect women all over the world from HPV infections, cervical cancer incidence would fall drastically. Thus my proposed solution in this report is the human papillomavirus (HPV) vaccine.

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The Solution: Human Papillomavirus (HPV) Vaccine

Introduction to HPV Vaccine

Cervical cancer is essentially a rare, long-term outcome of HPV infection. In fact, almost every case of cervical cancer is associated with high-risk HPV types as can be seen below. If infection by high-risk HPV types were wiped out through vaccination, this would provide an exciting prospect for prevention of cervical cancer.

Cervical cancer is caused by persistent infection by high-risk HPV types, including HPV 16, 18, 31, 33, 35, 45, 51, 58 and 59. HPV 16 and 18 collectively are responsible for approximately 70% and HPV 16, 18, 45, 59 and 35 account for about 95% of all cervical cancers.

Malaysian Immunisation Manual, 2008 2

Vaccination is the inoculation of vaccine virus to render individuals immune to a specific disease. 2 At present, there are 2 types of HPV vaccines developed commercially: GARDASIL ®, a tetravalent vaccine against types 6, 11, 16 and 18 developed by Merck; and CERVARIX ®, a bivalent vaccine against types 16 and 18 developed by GSK.4,5

Current HPV vaccines are generally used for uninfected females, specifically, for girls and women aged 9-26.23 Vaccination should precede sexual activity for maximum effectiveness, that is, before exposure to HPV. 14

HPV vaccination greatly reduces the risk of being infected by genital warts and cervical cancer. With that in mind, women should be aware that the vaccination does not protect against all types of HPV nor all cases of cervical cancer. Also, it is important to note that the vaccine is prophylactic and not therapeutic, that is, it will prevent against future HPV infections but will not treat existing ones.9, 23, 24

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Biology of HPV Vaccine

Diagram 4: Human Papillomavirus (HPV)


HPV is a member of the Pappilomavirus family. Each virus consists of a double stranded DNA enclosed within a capsid shield, composed of two protein molecules: L1 and L2. More than 100 types of HPV have been identified, classified into low-risk (non-cancer associated) and high-risk types (cancer associated).2 HPV is the most common sexually transmitted virus, as 80% of sexually active women will have an HPV infection in their lifetimes.3

CERVARIX contains recombinant C-terminally truncated L1 proteins from HPV type-16 and type-18. The HPV-16 and HPV-18 L1 antigens are prepared by recombinant DNA technology. The adjuvant used is ASO4.4

CERVARIX official product information

GARDASIL is a quadrivalent vaccine prepared from purified virus-like particles (VLPs) of the major capsid (L1) protein of HPV types 6, 11, 16 and 18. The adjuvant used is Amorphous Aluminium Hydroxyphosphate Sulfate.5

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GARDASIL official product information

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L1 VLPs used in the vaccines are structurally indiscernible from HPV virions and stimulate active immunity but do not contain viral DNA thus are uninfectious.25 Upon vaccination, HPV antigens introduced to the body produces a strong immune response. This induces generation of memory B-cells and T-helper cells, which are important for rapid generation of neutralizing antibodies.10 L1 antibody is the most immunogenic of neutralizing antibodies against various viral capsid proteins.2

Transmission of HPV occurs at the cervical epithelium. High serum L1-IgG antibodies in immunized persons produce transudated L1-IgG antibodies in the cervical mucus which bathes the cervical portio and upper vaginal epithelium.2 The antibodies bind and neutralize virus particles, preventing HPV adhesion and invasion.10 Recipient is then protected from certain types of HPV infection and indirectly, cervical cancer.

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Efficacy of HPV Vaccine

Both vaccines, CERVARIX and GARDASIL, are highly immunogenic over a wide age range. After 3 doses of the vaccine given at 0, 1 and 6 months, 98% of the recipients developed neutralizing antibodies which were up to 11 times higher than natural antibody levels following an infection.2 Official product information from GSK shows that protective antibodies were sustained for at least 7.3 years (to date) and modeling predicts the antibodies will remain detectable for at least 20 years, as shown in Diagram 5.4 This suggests that recipients will be protected from HPV-16 and HPV-18 for to 20 years.

Diagram 5: CERVARIX Official Product Information3

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The efficacy of CERVARIX was assessed in two controlled, double-blind, randomized Phase II and III ongoing clinical studies that included 19778 women. As shown in Table 1, there were no cases high-grade abnormalities, hence showing absolute prevention of further development into cervical cancer. 4

Event Type


Number of Subjects

Number of Cases

% Efficacy

Incident Infection








Persistent Infection

























Table 1: Vaccine Efficacy (Cohort: Oncogenic HPV-naïve population) 4

The efficacy of GARDASIL was assessed in 5 double blind randomized Phase II and III clinical studies, involving 24596 individuals (20541 girls and women, and 4055 boys and men). In summary, GARDASIL was almost 100% efficacious against HPV disease caused by HPV types 6, 11, 16 and 18 in girls and women, as shown in Table 3.5

Event Type


Number of Subjects

Number of Cases

% Efficacy

HPV 6-, 11-, 16-, or 18-related Genital Warts








HPV 6-, 11-, 16-, or 18-related CIN








Table 2: Vaccine Efficacy (Cohort: Total Vaccinated, Oncogenic HPV-naïve) 5

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Implications of HPV Vaccine


The HPV vaccine places a large financial burden on both society and public expenses. There is no doubt that mass vaccination of females worldwide is a noble goal but the high cost of immunization is a major consideration. For example, Kenyan director of health promotion in the Ministry of Health Nicholas Muraguri acknowledges that at the cost of USD300 (more than the average annual income for a family), many Kenyans will be unable to afford the vaccine. 18 Although the current HPV vaccine is covered by public expenses in some countries (US, UK, Australia etc.), the public health sectors in a majority of low-resource countries cannot afford mass inoculation.6 Consequently, the HPV vaccine is available only in the private sector in many countries for those who can afford them. I feel that this divide based on financial ability prevents the vaccine from reaching those who need it most, namely impoverished women in low-resource countries who are unable to attend regular cervical cancer screening.


Opponents of the HPV vaccine say that the vaccine will encourage sexual promiscuity in adolescents.12, 13, 14 Unlike common childhood vaccines like polio and measles, HPV is a sexually transmitted disease. For this reason, there are fears that the HPV vaccine will give teenagers a false sense of security against infection by various STDs, leading to sexually risky behavior. Reginald Finger, a former medical advisor to Focus on the Family, told The Hill that "if people begin to market the vaccine as something that makes adolescent sex safer, that that would undermine the abstinence-only message".19 On the other hand, it is highly unlikely that vaccination against HPV will influence a teenager's sexual directions. In any case, "opposing an effective vaccine that would save hundreds of thousands of women's lives with the vacuous assertion that it would lead to promiscuity is inexcusable," said National Organization for Women President Kim Gandy.19

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Benefits and Risks

The HPV vaccine, the first ever vaccine designed to prevent cancer, has been hailed as a medical triumph. CERVARIX and GARDASIL immunize recipients against HPV types 16 and 18 for at least 6 years and possibly up to a lifetime. With the introduction of the vaccine, cancer associated with HPV16/18 could be reduced by up to 95% while other HPV related diseases would also decrease, saving thousands of lives. 12 Accordingly, the associated psychosocial and economic burden would diminish.

Additionally, herd immunity dictates that vaccination of a significant portion of the population will protect the entire community. Hence if enough of the population were protected, HPV 16 and 18 could be totally eradicated, further protecting the world's population from cervical cancer.

To eradicate HPV 16 and 18, at least 90% of the population would have to be vaccinated.

Eliav Barr, M.D., head of Merck's HPV vaccine program24

The safety of the vaccines has been tested with extensive clinical trials. Adverse reactions occurring after vaccination include local pain, swelling and fever. There have also been incidents of fainting after vaccination thus patients are advised to remain under observation for 15 minutes. Generally, most side effects were well tolerated. 2

Nevertheless, it is a fact that the HPV vaccines are relatively new vaccines and we do not yet know their long term effects. For example, other HPV strains might emerge as oncogenic serotypes when HPV 16 and 18 are effectively suppressed.13 Also, if immunity wanes and infection with high-risk HPV occurs at a later age, the infection might not progress as expected.2

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There is also a risk that the HPV vaccination may cause less participation in screening tests. In my opinion, recipients must be made aware that they are not completely immune from cervical cancer. It is significant that women who neglect cervical cancer screening will increase their risk of cervical cancer. Until a multivalent vaccine targeting all oncogenic HPV types is introduced, regular cytology screening is still the best cancer prevention strategy and should be recommended to all women of suitable age.25

Alternative Solutions for Prevention of Cervical Cancer

Abstinence and Education

Total abstinence from sexual activity and direct genital contact is the only way to completely prevent HPV infection.2, 23 However, this is an unrealistic solution to minimize the risk of cervical cancer. Of course, staying in a mutually faithful relationship and limiting one's number of sexual partners lowers the risk of HPV as well. Condoms may lower the risk of HPV infection, but is not completely effective due to the high prevalence and easy transmissibility of the HPV virus.2 In my opinion, health education programmes promoting abstinence, monogamy and safe use of condoms would lower the spread of HPV in society.

The only sure way to prevent HPV is to abstain from all sexual activity.

Centre of Disease Control and Prevention (CDC) 23

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Cytologicy Screening (Pap Smear)

Regular Papanicolaou smears (cervical cytology screening) is an important step in the prevention of cervical cancer.25 Pap tests look for abnormal cells in the cervix that may progress to cancer. The cervical smear involves taking a sample of cells from the cervix and sending it to a lab for microscopic examination. Women should have a Pap test once every 2 or 3 years.26 The Pap smear is one of the most reliable cancer-screening tests available and should still be performed even after vaccination. As an illustration, the cervical cancer morbidity in the UK fell from 2000 in 1988 to 921 in 2006 after introduction of a population screening program in 1988.16 In Malaysia, I think that a complementary program of vaccination and Pap smear screenings should be introduced throughout the country, with special emphasis on rural regions. It is important to remember that vaccination alone is not sufficient to prevent all types of HPV infection.

Diagram 6: Pap Smear


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Evaluation of References

The Malaysian Immunization Manual (2008) [2] is the definitive guide to vaccines published by the Academy of Medicine Malaysia. In my opinion, the chapter on the HPV vaccine is inclusive and well researched, as well as very reliable as it is used by doctors and health professionals throughout Malaysia. Subtopics include both the clinical disease (HPV infection) and immunization (HPV vaccine), with sections on epidemiology, prevention and recommendations. These were well-supported by official product information from GSK and Merck. [3, 4, 5].

The journal article 'The ethics and politics of compulsory HPV vaccination' by James Colgrove (2006) [13] discusses reactions to mandatory vaccination from an ethical and political viewpoint. The journal article was published in The New England Journal of Medicine, the oldest, most widely-read and influential peer-reviewed medical journal in the world thus is very valid. I found the journal very clear and informative as it provided information on reasons for rejection of the HPV vaccination, including religious views and safety concerns. This information was supported by other articles [19, 20, 21] and journals [12, 14].

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