Human Papilloma Virus Vaccine : Future of Cervical Cancer Prevention

Cervical cancer is a deadly cancer that clutches lives of the women in most of the cases due to lack of consciousness about the disease in the developing countries. It remains a threat which is second only to breast cancer in overall disease burden for women throughout the world. Cervical cancer is almost a preventable disease by prophylactic vaccine and routine screening. Both Cervarix and Gardasil vaccines have been effective in preventing persistent infection with targeted HPV types and in preventing cervical intraepithelial lesions. It is safe and nearly 100% effective if given before onset of sexual activity. This review article is aimed to explore different aspects of this vaccine as well as to develop awareness among health professionals of different disciplines. J Enam Med Col 2016; 6(3): 157-160

Cervical cancer remains a critical public health problem that is second only to breast cancer in overall disease burden for women throughout the world. 1 It is still an important cause of mortality and morbidity in the developing countries. 2Universal deployment of organized or opportunistic screening with Pap cytology in high and middle income countries has been the primary reason for the substantial reductions in cervical cancer morbidity and mortality during the last 50 years.However, in many low income countries Pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. 3Screening appears to benefit only a small fraction of women although a much larger percentage endures the inconvenience of the Pap test in order to avoid cervical cancer. 2man papilloma virus (HPV) infection is one of the most common sexually transmitted diseases worldwide.Up to 79 million of sexually active women worldwide will become infected with HPV during their lifetime. 4o date, more than 120 genotypes of Human Papilloma virus (HPV) are known, but only high risk oncogen genotypes could induce a cancer.HPV 16 and 18 are implied in nearly 70% of cervical cancer around the world. 5In Bangladesh, the annual number of cases of cervical cancer is 1 1 956 and death is 6 582. 6A prophylactic vaccine to protect against the precancerous and cancerous lesions associated with HPV should save lives, reduce expensive diagnostic and t herapeutic interventions, and have substantial individual and collective benefits. 5In this review paper, we discuss the type of cervical vaccine and its mechanism of action.Various reports of trial and vaccine impact on different categories of women are also discussed.

157
closely r e semble the natural virus, and antibodies against the VLPs also have activity against the natural virus.The VLPs have been found t o b e strongly immunogenic, which means that they induce high levels of antibody production by the body. 7The antibody induces more than 90% protection from persistent HPV 16, 18 infection and HPV 16 and 18 associated high grades cervical intraepithelial neoplasia. 8HPV 16 and 18 vaccination will prevent HPV 16, 18 infection, and subsequently decreases in 90% t he frequency of abnormal Pap attributable to t hese types.HPV vaccination will reduce the number of women who require colposcopy, biopsy and cervical treatment for precancerous cervical lesions. 1

Types of vaccine
Three vaccines are approved by the FDA to prevent HPV infection: Gardasil, Gardasil 9, and Cervarix.All three vaccines prevent infections with HPV types 16 and 18, two high-risk HPVs that cause about 70% of cervical cancers and an even higher percentage of some of the other HPV-associated cancers. 9Gardasil also prevents infection with HPV types 6 and 11 which cause 90% of genital warts. 10Because Gardasil protects against infection with four HPV types, it is called a quadrivalent vaccine.Gardasil 9 prevents infection with the same four HPV types plus five additional high-risk HPV types (31, 33, 45, 52, and 58) and is therefore called a nonavalent, or 9-valent vaccine.All t hree vaccines are given through a series of three injections into muscle tissue over a six months period (0 month, 1 month and 6 month or 0 month, 2 month and 6 month) and the need for boosters is unknown. 11The best age for primary vaccination appears to be 11-12 or 14 years, before the onset of sexual activity. 12The FDA has approved Gardasil and Gardasil 9 for use in females aged 9 through 26 for the prevention of HPV-caused cervical, vulvar, vaginal and anal cancers, precancerous cervical lesions and genital warts.Gardasil and Gardasil 9 are also approved for use in males for the prevention of HPV-caused anal cancer, precancerous anal lesions and genital warts. 13It targets two HPV types -16 and 18 and is called a bivalent vaccine.The FDA has approved Cervarix for use in females aged 9 through 25 for the prevention of cervical cancer caused by HPV.Both vaccines have a known duration of protection of at least 5 years; clinical trials are still in progress to show the full duration of protection. 13

Side effects
Side effects include pain, redness or swelling at the injection site, mild fever and itching at the injection site.However, these symptoms do not last long and life-threatening allergic reactions from vaccines are very rare. 14

Women with previous c e rvical i n traepithelial neoplasia (CIN)
The vaccine can be given to patients with previous CIN, but the benefits may be limited to the protection against infection of HPV genotypes (and related CIN) with which they have not been infected and this vaccine is not for treatment.It must be emphasized that cervical cytology surveillance and corresponding management must continue. 15

Pregnancy and lactating women
The use of t he vaccine in p r egnancy is not recommen-ded although no teratogenic effect caused by the vaccine has been reported.There is no evidence to show that the HPV vaccine adversely affects fertility, pregnancy or infant outcome.

Immunosuppressed patients
Immunosuppression is not a contraindication t o vaccination.However, the immune response to the HPV vaccine may b e less competent in t hese women compared with a healthy individual. 17

Contraindications and precautions
The HPV vaccine is contraindicated for people with a history of hypersensitivity to any vaccine component.Va c cination of people with moderate or severe acute illnesses should be deferred until after the illness improves. 16

Cervical c a ncer a n d v accine status i n developing countries
Cervical cancer is the most prevalent cancer that continues t o b e a m ajor health care problem worldwide and it is still an important and common gynecological cancer in the developing countries.
Cervical cancer constitutes about 21-23% of the female cancer in different areas of India and Bangladesh. 2 Bangladesh stands 11 th for cervical cancer fatalities in the world.Data collected from different hospitals reveal that cervical cancer is the commonest cancer in Bangladesh. 18Prevalence of cervical cancer is also high in other developing countries like Senegal, Madagascar, Malawi, Nigeria and Sierra Leone.This high prevalence of cervical cancer is r e lated t o m any r isk factors as e arly marriage, early starting of sexual activity, multiparity, low socioeconomic condition and high incidence of sexually transmitted diseases and HPV infection. 19t only the different risk factors for cervical cancer but also the price of vaccine is the other main factor.The retail price of the vaccines is approximately $130 to $160 per dose worldwide. 20It is really impossible for low income countries to afford this price.But according t o Global Alliance for Vaccines and Immunization (GAVI), more than 85% of the 275,000 global deaths every year due to cervical cancer are in low-income nations.The HPV vaccine is available for routine immunization in relatively wealthy countries until now.But recently, GAVI has announced that they have already outlined plans to introduce HPV vaccine in routine immunization program with record low price for the low income countries -$4.5 per dose. 20n Bangladesh, Cervarix vaccine is available and manufactured by GlaxoSmithKline (GSK).It contains two HPV types -16 and 18.

Vaccine efficacy
HPV vaccines are highly e ffective in p r eventing infection with the types of HPV they target when given before initial e xposure to the virus, which means before onset of sexual activity.In a combined analysis of the initial efficacy and extended follow-up studies, vaccine efficacy of 100% against cervical intraepithelial neoplasia (CIN) lesions is associated with vaccine types. 4In another study that led to approval of Gardasil and Cervarix, these vaccines were found t o p r ovide nearly 1 0 0% p r otection against persistent cervical infections with HPV types 16 and 18 and t he cervical cell changes t hat these persistent infections can cause. 21A clinical trial of Gardasil in men indicated that it can prevent anal cell changes caused by persistent infection and genital warts. 22Although these two vaccines give 5-year protection, long-term studies of vaccine efficacy t hat are still in p r ogress will help scientists b e tter understand t he total duration of protection.

Conclusion
In conclusion, cancer cervix is a potentially preventable disease.But due to lack of proper knowledge about disease and vaccine, it is still a major health problem and burden to the developing countries.HPV vaccination of girls before sexual debut could be a potential tool for the prevention and control of cervical cancer.According to GAVI, if it is possible to introduce vaccine in routine immunization program with low price in low income countries and if p r oper screening is done at the precancerous stage, in future the rate of cervical cancer will decrease to a greater extent.

G
Women who are planning to conceive are advised to defer vaccination until after delivery.GWomen who become pregnant before completion of vaccination are advised t o p ostpone the remaining dose until after the pregnancy.GTermination of pregnancy is not indicated for women who b e come inadvertently p r egnant during the course of vaccination.G Lactating women can receive the HPV vaccine and still continue breastfeeding because it is a vaccine without live viral DNA.