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 Table of Contents  
REVIEW ARTICLE
Year : 2016  |  Volume : 3  |  Issue : 4  |  Page : 252-257

Human papillomavirus vaccination: Review and roll out plan in Delhi


1 Department of Community Medicine, North Delhi Municipal Corporation Medical College and Hindu Rao Hospital, New Delhi, India
2 Department of Respiratory Medicine, Employees State Insurance Corporation Medical College, Faridabad, Haryana, India

Date of Web Publication14-Sep-2016

Correspondence Address:
Dr. Sandeep Sachdeva
Department of Community Medicine, Hindu Rao Hospital and North Delhi Municipal Corporation Medical College, New Delhi - 110 007
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2348-3334.190584

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  Abstract 

This manuscript reviews and describe the burden of cervical cancer in world and India, epidemiology of HPV infection, screening methods, prevention, control strategy, types of HPV vaccines, schedule, age of administration, dose, route, anatomical site of human papillomavirus vaccination, cold chain, vaccine coverage and roll out plan in Delhi, India.

Keywords: Adolescent, cervical cancer, epidemiology, immunization, malignancy, prevention, program, women


How to cite this article:
Sachdeva S, Sachdeva R. Human papillomavirus vaccination: Review and roll out plan in Delhi. CHRISMED J Health Res 2016;3:252-7

How to cite this URL:
Sachdeva S, Sachdeva R. Human papillomavirus vaccination: Review and roll out plan in Delhi. CHRISMED J Health Res [serial online] 2016 [cited 2020 Apr 2];3:252-7. Available from: http://www.cjhr.org/text.asp?2016/3/4/252/190584


  Burden of Cervical Cancer Top


Globally, there were 14.1 million new cancer cases diagnosed during 2012 while 8.2 million died of cancer, and according to the estimate, 19.3 million new cancer cases would be diagnosed by the year 2025. The burden of cancer cases and deaths is high in less developed regions of the world, accounting for 57% of the total new cancer cases and 65% of global cancer deaths (GLOBOCAN 2012). Cervical cancer is the fourth most common cancer in women with an estimated 528,000 new cases in the world, with estimated 266,000 deaths accounting for 7.5% of all female cancer deaths in the year 2012. India accounted for 23.2% (123,000) of new global cervical cancer cases and 25.1% (67,000) of cervical cancer-related deaths.[1] The age-standardized incidence of invasive cervical cancer in India is 27 and mortality of 15.2/100,000 women.[2] [Figure 1] depicts age-standardized cervical cancer incidence rate across the globe (World Health Organization [WHO]). Over the past three decades, cervical cancer rates have fallen in most of the developed world largely as a result of organized screening and treatment programs reaching larger segment of population albeit at a cost. In contrast, rates in most developing countries have risen or remained unchanged. Ninety percent of cervical cancers is squamous cell cancers and the other 10% is adenocarcinoma.[3],[4],[5]
Figure 1: World map showing the incidence of cervical cancer, 2012 (age-standardized rate per 100,000 women)

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  Epidemiology and Virology of Cervical Cancer Top


Human papillomavirus (HPV) is one of the most common viral infections of the reproductive tracts of both females and males. Based on a meta-analysis, the adjusted HPV prevalence worldwide among women with normal cytological findings was estimated to be 11.7% (95% confidence interval: 11.6–11.7%).[6] Up to 80% of women acquire an HPV infection in their lifetime.[7] The prevalence figures in men are limited; a systematic review of genital HPV among men in sub-Saharan Africa found prevalence of any HPV type between 19.1% and 100%.[8] Approximately 200 HPV genotypes (types) have been described.[9] However, persistent infection by oncogenic HPV types 16 and 18 is responsible for the development of cervical cancer. Together, these two types account for around 70% of cervical cell carcinomas.[10] HPV infections cause several different cancers including vaginal, vulvar, penile, oropharyngeal, and anal cancers.[11]

In addition, HPV types 6 and 11 cause anogenital warts and recurrent respiratory papillomatosis. Cervical cancer occurs only in a small fraction of those infected as majority of subclinical HPV infection resolves on itself while in smaller proportion it persists and takes further 10–20 years to develop into cancer. It is estimated that no more than 2% of all women in low-resource countries will develop cervical cancer during their lifetime. The risk of developing squamous cell carcinoma of the cervix is about 400 times higher following infection with HPV-16 and about 250 times higher following infection with HPV-18 compared to the risk in uninfected women.[12]


  Prevention and Control Strategy Top


Compared with diseases attributable to noninfectious causes, it is often easier to prevent or treat diseases caused by infectious agents. The identification of HPV as the infectious agent responsible for cervical cancer in the early 1980s by zur Hausen was hailed as a major advances.[13] This fundamental discovery was followed up by additional research resulting in the development of vaccines and other screening methods. Comprehensive prevention and control strategies include prevention with HPV vaccination for young girls, screening and treatment for women diagnosed with precancerous lesions, and treatment and palliative care for women with invasive cervical cancer. Screening for precancerous lesions can be done in several ways including cervical cytology (Papanicolaou-test), visual inspection of the cervix with acetic acid (VIA), or testing for HPV DNA. Each of these strategies has specific advantages, weakness, and health system requirements while mainstay in low-resource setting is VIA strategy. [Table 1] depicts sensitivity and specificity of various screening methods.[14]
Table 1: Screening methods for cervical cancer

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Vaccination with HPV types may not result in protection of all recipients, and the women subjects receiving complete immunization schedule would still be advised to undergo age-appropriate screening for premalignant lesions. The long-term benefit of vaccination would be accrued only when at least 75% of the targeted preadolescent population is covered by prophylactic vaccination. Research has proved that vaccinating preadolescent girls, viz., boys, is more cost-effective strategy in preventing cervical cancer in later life. Health education, personal hygiene, male circumcision, and tobacco control would further lead to reduction of cervical cancer burden.[15] Details are shown in [Table 2].
Table 2: Prevention and control of cervical cancer over the life course

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  Global Status of Human Papillomavirus Vaccination Top


The WHO recommends that HPV vaccination to be introduced in the national immunization program considering disease burden and cost-effectiveness strategy. More than 63 (32.6%) countries in the world have introduced HPV vaccine in their national immunization schedule by the end of 2014.[16] Efforts are being made to roll out HPV vaccine in other countries with financial assistance from global alliance for vaccine and immunization (GAVI). [Figure 2] depicts world map showing countries with introduction of HPV vaccine in their national health program for girls, especially developed countries and other GAVI supported vaccine roll out countries (Source: Program for Appropriate Technology in Health [PATH], 2015). Australia, the first country in the world to introduce HPV vaccine in National Immunization Program for girls during 2007, has consistently recorded coverage of three doses of HPV vaccine among 70% of females aged 15 years and above since 2009.[17] In the United States, for the year 2014, girls aged 13–17 years who received at least one dose of HPV vaccine was 60.0% (3.3% points higher than 2013 figure) while only 39.7% completed the three dose schedule.[18]
Figure 2: World map showing countries with human papillomavirus vaccine introduced in the National Health Program

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  Type of Human Papillomavirus Vaccine Top


The two prophylactic first-generation HPV vaccines, quadrivalent HPV type 6/11/16/18 vaccine and bivalent HPV type 16/18 vaccine, were licensed in 2006 and 2007, respectively, under the names of Gardasil ® Silgard ® (Merck and Co., Inc, NJ, USA) and Cervarix ® (GlaxoSmithKline, Brentford, London) and the second-generation 9-valent HPV type 6/11/16/18/31/33/45/52/58 vaccine with broader cancer coverage has also received the US Food and Drug Administration approval in December 2014 under the name of Gardasil 9® (Merck and Co, Inc.). Quadrivalent and 9-valent HPV vaccines are licensed for use in females and males while bivalent HPV vaccine is licensed for use in females only. Gardasil prevent cervical, vulvar, vaginal, anal cancer, precancerous or dysplastic lesions, and genital warts. By preventing HPV infection and disease due to HPV31/33/45/52/58, the 9vHPV vaccine has the potential to increase prevention of cervical cancer from 70% to 90%. In addition, the 9vHPV vaccine has the potential to prevent 85–95% of HPV-related vulvar, vaginal, and anal cancers. These vaccines are prophylactic in nature, i.e., they do not treat the underlying cervical lesion.[19],[20],[21],[22],[23] Both vaccines are intended to be administered before the onset of sexual activity, i.e., before first exposure to HPV infection. There are no adverse effects observed among females and offspring, yet data are limited therefore not recommended for pregnant mothers. Using recombinant technology, both generations of vaccines are prepared from purified L1 structural proteins that self-assemble to form HPV type-specific empty shells or virus-like particles. Neither of these vaccines contains live biological products or viral DNA, and both are therefore noninfectious; they do not contain any antibiotics or preservative agents.


  Schedule, Dose, Site, and Route of Human Papillomavirus Vaccine Administration Top


Appropriate age, dose, schedule, route, site of administration, and cold chain preservation of vaccine are shown in [Table 3].[24] A recent published research lends support to two-dose regimen at least 6-month apart for routine vaccination of young girls, and the short-term protection afforded by one dose of HPV vaccine against persistent infection with HPV 16, 18, 6, and 11 is similar to that afforded by two or three doses of vaccines but merits further assessment.[25] Mathematical models have shown in high-income countries that a two-dose vaccination conferred more than 10–20 years protection. Furthermore, clinical trials are ongoing to evaluate alternative/reduce dosing schedules for 9vHPV.[25] Each manufactured vaccine is produced in a unique manner, and hence, once started with a particular brand of vaccine, ideally should be completed with the same type of vaccine. However, in case of non-availability or nonawareness of type of first vaccine, switch over to any type is advised to complete the immunization series. Follow-up trials have shown that protection against HPV lasts for at least 5 year postvaccination for the quadrivalent vaccine and 6.4 years for the bivalent vaccine.[26],[27] However, booster dose is not recommended as these vaccines behave similar to hepatitis B virus vaccine where titers per se may not be measurable, yet immune memory exists and shows anamnestic effect.[28] The HPV vaccine needs to be shaken well before administration and can be safely co-administered along with other vaccine such as hepatitis B at different sites in human body using separate injection/syringe. All HPV vaccines are freeze-sensitive and should be preserved at 2–8°C only. Contraindications to vaccine include hypersensitivity/allergic reactions to yeast or with previous dose of vaccine especially Gardasil 9 and Gardasil. Up to 80% recipient may develop local adverse effects such as injection site pain, swelling, and erythema. The other less common side effects include fever, nausea, and dizziness. Each subject after receiving vaccine should be observed for at least 15 min since they may rarely also develop syncope/fainting episode or anaphylaxis (rate, 1.7–2.6/106 doses).[29]
Table 3: Human papilloma virus vaccination schedule

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  Status of Human Papillomavirus Vaccine and Coverage in India Top


The Indian Academy of Pediatrics recommended inclusion of HPV in its immunization schedule way back in 2007, and more robust reaffirmation for inclusion was made recently also.[30] HPV vaccines were licensed in India by the Drug Controller General of India in 2008–2009. Lot of academic, medical, public health, advocacy groups, nongovernmental organizations and parliamentary discussion, debate arguments, and scientific publications have happened for and against [31] starting of population based mass HPV vaccination in the country. HPV vaccine delivery and demonstration project in Andhra Pradesh and Gujarat led by an international nonprofit organization, PATH, was proposed for the interim period 2009–2011 but suspended in 2010 due to public concern, controversy, social and political pressure arising from death of girls who received HPV vaccine.[32],[33] Subsequent investigations proved that these deaths were not linked to vaccination. However, the project further could not see the light of the day but collaterally led to the development of more stringent regulatory, ethical, quality control and monitoring environment of health and human research in country. This event further reinforced the importance of health communication, consequence of negating and poor management of rumor and misinformation in community, confidence, trust buildup, and involvement of multiple stakeholders in decision-making process.

The licensed vaccine was available in project sites for free and private sector in the country at a very high cost albeit scantily. Since there is no vaccine coverage data available other than project sites, in all probability, vaccine coverage is negligible at national level considering awareness, access, availability, cost, risk, and safety concern issues. Vaccine delivery strategy at project site (Andhra Pradesh-Khammam District and Gujarat-Vadodara District) included school and health center-based delivery with delivery either at three fixed time points (i.e., campaign approach) or routine delivery approach. Nearly 27,169 girls through the age group of 10–14 years were eligible to receive vaccine within and outside school purview at both sites. The study on complete vaccine (three doses of HPV) coverage revealed that campaign approach achieved 77.2–87.8% coverage whereas monthly delivery achieved 68.4–83.3% in the project sites.[34]

Several private sector organizations such as the Indian Immunologicals Ltd., Hyderabad; Shantha Biotechnics Ltd., (wholly owned subsidiary of Sanofi), Hyderabad; Bharat Biotech Interl Ltd., Hyderabad; Serum Institute of India Ltd., Pune; Gennova Biopharmaceuticals Ltd., Pune; and Virchow Biotech Pvt. Ltd., Hyderabad, and also public sector organizations such as Translational Health Science and Technology Institute, Gurgaon, Haryana; and Institute of Cytology and Preventive Oncology, Noida, Uttar Pradesh, are actively involved in HPV vaccine development in India.[35]


  Roll Out Plan in Delhi Top


Delhi, the National Capital of Country, has a certain unique set of characteristics due to historical background, high connectivity, large-scale migration, varied sociocultural-religious-economic-political environment, combination of urban, urbanized-rural and slum population residing in nine administrative zones. For the purpose of milestones to name a few, Delhi was the first state in the country to initiate pulse polio campaign (1995) and hepatitis B immunization for infants (partly in 1998 and fully in 2004) in project mode, etc. In the current context, the Government of Delhi in 2016 has announced that HPV vaccine to be included in immunization schedule of state for administration of adolescent girls, again a first in the country.[36] This will be introduced in a phased manner, targeting firstly the girls studying in class sixth of government schools in age group of 9–13 years with two doses. The vaccine will be imported from outside the country since currently it is not produced in India but at a subsided cost of Rs. 450/- against the market price of Rs. 3000/- per dose.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]


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