Correspondence:
Dr. Ebtisam Elghblawi
Email: ebtisamya@yahoo.com

About 9710 women in the USA annually are diagnosed with cervical cancer according to the American Cancer Society (ACS, 2006). About 20 million cases are infected with HPV worldwide, out of which about 6 million are American and about 400,000 in the developing world itself, with about 290,000 dying of cervical cancer worldwide annually (Stella Heley, 2007). According to CDC (Center of Disease Control and prevention), it is estimated that by age 50, about 80% of women will have genital HPV infection.

Finland and Australia is well known to have the lowest cervical cancer rate in the world, due to the national screening program. Australia has the second lowest record in the world, by about 60%, since the introduction of the national screening program in 1991 About 700 women are diagnosed each year and about 240 die. This is due to either not having a Pap test in the past 10 years, or being inadequately screened, and around 75% were over 50. 80% of cervical cancers are caused by HPV 16 and 18.

HPV is responsible for 99.7% of cervical cancer, 90% of genital warts, 70% of anal cancer, 50% of penile cancer, and about 25% of oropharyngeal cancers (Anonymous, 2006, Abby Lippman, Ryan Melnychuk, et al, 2007, Jenny may, 2007). HPV is a DNA virus which exhibits about 200 different strains classified according to DNA sequences, and about 30 are known as Sexually Transmitted Viruses (Judy Norsigian; Alicia Priest; Robin Barnett, 2007, Jenny may, 2007, Stella heley, 2007), and 40% are anogenital strains with 15 high risk types (oncogenic); HPV 16, 18, 31 &45. HPV types 16 and 18 are considered to be of high potential risk (70%) for developing cervical cancer worldwide, and 50% high-grade lesions; especially high-grade squamous intra-epithetial cancer, and cervical intra-epithetial cancer, while HPV 31 and 45 cause 10% of the cancer, and affect both the male and female genital area (Joanna Breitstein, 2006, Cormac Sheridan, 2007, Maryann Napoli, 2007), whereas type 6, 2 and 11 are low risk and blamed for 90% of genital warts, with 10% low-grade cervical lesions (Jenny May, 2007, Chemist & Druggist, 2007, Stella Heley, 2007).

HPV is the commonest Sexually Transmitted Disease (STD) and is highly infectious with 50% transmission rate post exposure (Jenny may, 2007). It's a common sexually transmitted disease , and it enters the skin through tiny micro-abrasions, where it remains confined to the surface epithelium, then enters the nucleus of the basal cell (Alicia Priest, 2006, Jenny May, 2007, Stella Heley, 2007). Then it relies on the replication of these cells, and its transformation, then exfoliation, and then spread. Via Pap smear those exfoliated cells are collected, and examined for certain features such as dense or double nucleus, or high nuclear-cytoplasmic ratio (Stella Heley, 2007). The immune cells cannott find it in order to fight it because HPV hides very well from the immune system. HPV is a very common infection in the first 10 years of establishing sexual activity. The first infection is sub-clinical, and what is called (common cold), and usually HPV infection clears within a year in about 70% (Judy Norsigian; Alicia Priest; Robin Barnett, 2007, Jenny May, 2007, Stella Heley, 2007). There is no actual test to trace the clearance rate nor to suggest developing the actual cancer (Alicia Priest, 2006). Every active sexual woman will has at least one HPV infection in her lifetime, and the infection resolves on itsown so no-one can know if they are infected (Alicia Priest, 2006).

The WHO predicts a rise in mortality rate up to 25% over the next coming 10 years (Alicia Priest, 2006). The WHO is interested in including the vaccine in its essential medicine but the high costs, and the short supply remains a big obstacle. Also in the USA some conservative groups are opposed to making the vaccine a mandatory issue, and therefore their permission is needed for their girl's vaccination, as this will reflect a false message for safe sex, and encourage promiscuity (Maryann Napoli, 2007, Gill Jenkins, 2007). From the sex concept, the more partners a person has, the greater the HPV risk of infection (Alicia Priest, 2006).

HPV is a marker of sexual activity, and not everyone will develop cervical cancer. HPV is associated with poverty, poor nutrition, smoking, lack of education, low standard of living, all of which compromises the immune system and thus HPV persists and so cervix cancer can occur (Maryann Napoli, 2007, Judy Norsigian; Alicia Priest; Robin Barnett, 2007).

Cervical cancer is 90% preventable with Pap screening and treatment. Therefore this brings up the necessity of a Pap test, which after its introduction has dropped the cervix cancer rate by 75%. It is a simple screening tool for cervical cancer. It is carried out routinely in some countries such as the UK, and not available yet in the developing countries where women are still dying of a preventable disease. The vaccine does not replace the routine cervical cancer screening Pap test (Judy Norsigian; Alicia Priest; Robin Barnett, 2007).
The cervical squamous changes occur at the squamo-columnar junction (Stella heley, 2007). This area is vulnerable to infection by HPV (Stella Heley, 2007). So the Pap test is aimed at picking-up this area with the cellular changes (Stella Heley). The squamous changes can vary between low-grade squamous intraepithetial lesions, or high-grade squamous intraepithetial lesions (previously known as CIN).

The old CIN term can be treated, in order to prevent progression to squamous cell cervical cancer (Stella Heley, 2007). If the smear reveals atypical cells, or a low-grade lesion, the body will defend itself via the immune system (Judy Norsigian; Alicia Priest; Robin Barnett, 2007). But those women with high-grade lesions should be followed by further testing. The glandular changes smear (columnar epithelial cells at endocervical canal) should be referred for colposcopy by an expert gynaecologist oncologist. Removal of the abnormal cells prevent invasive cancer in 90% (Judy Norsigian; Alicia Priest; Robin Barnett, 2007, Jenny May, 2007).

This quadrivalent HPV recombinant vaccine (Gardasil), was developed to combat and prevent cervical, and precancerous genital warts by producing neutralizing antibodies which bind tightly to the virus surface and prevent its attack on host cells (Alicia Priest, 2006, Angie L.Goeser, 2007, Anonymous, 2007). The non-infectious vaccine is composed of highly purified virus like particles (Jenny may, 2007). It is a white cloudy liquid given by intramuscular injection in three stages as is the case with hepatitis vaccine (Monica R McLemore, 2006). It cannot be given to pregnant women, and is not recommended for lactating women though there is no documentation yet regarding its excretion in milk. It is recommended for girls and women between 9-26 years (Barbara Sibbald, 2006, Anonymous, 2006, Angie L. Goeser, 2007). It should be shaken well before given The first dose is given, then two months later after dose 1 another, and finally six months after dose 1, yet another, in either the deltoid or upper antero-lateral thigh area (Angie L. Goeser, 2007). It is not known yet if a booster shot is needed.

The vaccine can be given concurrently with hepatitis, tetanus, reduced diphtheria, acellular pertussis, and meningococcal vaccines but not in the same syringe, or the same injection sites (FDA, 2006, Monica R McLemore, 2006, Angie L. Goeser, 2007, Jenny May, 2007). If the vaccine series is interrupted for one reason or another, it should be continued without restarting the whole series (Angie L. Goeser, 2007). There is no need to assess the HPV status before vaccination (Angie L. Goeser, 2007). The single dose costs $147, and the three-dose series $441 (Alicia Priest, 2006, drugs and herbs, 2006, Anonymous, 2006, Angie L. Goeser, 2007, Stella Heley, 2007). Side effects reported are pain, swelling, erythema, fever, nausea, naso-pharyngitis, dizziness, diarrhea, vomiting, myalgia, toothache, respiratory tract infection, malaise, arthralgia, insomnia, and nasal congestion (Monica R McLemore, 2006, Angie L. Goeser, 2007, Jenny May, 2007). It has been manufactured by Merk and Co., and has been offered int two forms: single-dose vials (0.5 ml), or single-dose, pre-filled, luer lock syringes (0.5ml). This vaccine should be refrigerated at 36-46 F, and should not be frozen. The main purpose for the vaccine is to prevent and not treat or cure those who have already contracted the HPV virus already (Alicia Priest, 2006, Jenny May, 2007). Also the vaccine would not work against other types other than HPV 1, 11, 16, and 18 (Monica R McLemore, 2006). It is not known how long the vaccine will protect, but protective antibodies persisted for about four to five years (Marc Iskowitz, 2006, Angie L. Goeser, 2007).

In June 2006 the FDA (U.S. Food and Drug Administration) has approved the first vaccine (Gardasil) for preventing cervical cancer, and genital warts in females between 9-26 years based on clinical trials (Marc Iskowitz, 2006, Barbara Sibbald, 2006, Jenny May, 2007). The CDC (Centers for Disease Control and prevention) recommended vaccination of those girls between 11-12 years of age before indulging in sexual activity, and it was added to the prevention vaccine program in 1 November 2006, and also it can be given to young females of 9-10 years before starting sexual activity (Angie L. Goeser, 2007, Jenny May, 2007). Catch-up vaccination is recommended for those who are 13 to 26 years (Angie L. Goeser, 2007). It is also advocated to vaccinate boys and young men between 9-15 years to prevent HPV infection with type 6, 11, 16 &18 but study on this is not yet completed, and maybe will be licensed later, plus the fact that men will be the natural community reservoir for HPV virus (Stella Heley, 2007, Meenakshi Dawar, Shelley Deeks, Simon Dobson, 2007, Gill Jenkins, 2007). The vaccine became available in Australia in August 2006. Australia is the 3rd country who have approved the vaccine after FDA in June 2006 (Stella Heley, 2007).
Also another new cervix bivalent cancer vaccine "Cervarix" has been launched in the UK in 2005, which is manufactured by GlaxoSmithKline (Natasha T Metzler, 2005). It has been estimated to be effective against two Human Papilloma virus; HPV 16 and 18, which are claimed to be the culprit for more than 70% of cervical cancer cases (Marc Siegel, 2006). This has been followed then by the vaccine "Gardasil" by Sanofi Pasture MSD in the UK in 2006, which is effective against HPV 6, 11, 16 and 18 (Natasha T Metzler, 2005, Pauline Comeau, 2007). It is actually developed by Merck in New Jersey; at the Whitehouse station (Cormac Sheridan, 2007). It is still not approved finally by the UK NHS, however some private sectors provide it (Marc Siegel, 2006, Anonymous, 2007).

According to Merck and Co. (drug manufacturers), Gardasil is the perfect guard, as it carries promising results in short terms; it has been targeted against the two common types of HPV (16 & 18), which are the main culprit of cervical cancer and genital warts. The trials were carried out on about 25,000 patients between 16-23 years in about 33 countries and the trial is in its Phase III, and showed 100% effectiveness (Kathie Lynas, 2005, Marc Siegel, 2006). It should be borne in mind that this vaccine would not protect against other HPV strains (research highlights, www.nature.com/reviews/cancer, 2005). The vaccine will provide protection against HPV 6, 11, 16 & 18.

The Gardasil vaccine's availability and implementation needs the work, the cooperation, and full engagement of stakeholders; whether media, opinion leaders, physicians, pharmacists, health workers, and the whole general populations to unleash the market for this vaccine. After all public health education campaign (safe sex, condom use, cervical cancer screening) is important rather than plugging in the vaccine without an explanation which will affect its acceptance from the public generally speaking (Abby Lippman, Ryan Melnychuk, et al, 2007).

Equally both Gardasil and Cervarix are extremely immunogenic; both induce high antibody titres that are many times higher than those induced by natural HPV infections, and this immunity lasts for about 5.5 years, (Meenakshi Dawar, Shelley Deeks, Simon Dobson, 2007).

The vaccination program should be built on tangible goals; for instance whether to eradicate the high-risk HPV types from the population, or to cut the death rate from cervical cancer, all of which need a different approach and strategy (Abby Lippman, Ryan Melnychuk, et al, 2007). In both cases thais implies considering vaccination of boys and young men in the former goal, and/ or directing Gardasil to all HPV types (broad ranges of oncogenic HPV) apart from considering the only two high-risk HPVs (16&18) in the latter goal (Abby Lippman, Ryan Melnychuk, et al, 2007).

The 9-13 years age group should be the priority target group for mass vaccination. vaccinated girls and women should still restrict themselves to safe sex practices, and consider the care program of Pap testing due to missing of effectiveness data regarding Gardasil, and it is still not confirmed yet how much the vaccine can add value, plus the fact that it only protects against some HPV types and not all (Anonymous, 2006, Abby Lippman, Ryan Melnychuk, et al, 2007). Finally there are still more questions than answers about HPV and Gardasil. Parents are now worried about the growing number of vaccines which are given to babies and young children.

It is essential to educate the public about cervical cancer and hence to cut down its incidence when possible, by considering the following points:

• Government should educate public about cervical cancer, HPV, genital warts, and Gardasil (Abby Lippman, Ryan Melnychuk, et al, 2007).
  
• Address the importance of healthy perssonel and safer sexual practices.
  
• Regular Pap testing for women.
  
• Screen for STDs.
  
• Cessation of smoking.
  
• Uphold unbiased research for evidence-based policy, and health care decision-making.
  

In developed countries Pap smear is the sole mandatory tool, in order to rule out any affected case, but on the contrary in developing countries this is still missing, and many cases go unnoticed. It is vital to develop a national immunization strategy to make certain a complete and systematic appraisal of all relevant factors before decisions regarding the implementation of a new immunization program are made. Also in order to halt cervical cancer, we needs improved reproductive health practices and the widespread availability of publicly funded programs for Papanicolaou smear testing, with follow-up testing for suspicious lesions.

After all it is not clear how much Gardasil will add in this aim, and how safet it is; unfortunately if something new has been discovered, tested and found to be working well, that does not imply it is correct; as, for example the story about the drug failure; COX-2 (Vioxx); when Vioxx was discovered before 2003 and had been announced widely and been used by many globally, and sometime later on it was revealed that it caused serious cardiac risks, and then withdrawals from the market began in 2003. In that case there should be always a warning before anything new is released, and on what basis.

It's also very important to consider the social and the cultural resistance in each country, and also to implement the vaccine before girls become sexually active, in order to save lives, especially in the developing countries. After considering the HPV strains, which are associated with cervical cancer development, and the fact that it can't protect against other HPV strains, the vaccine will reduce, rather than eradicate HPV infection and this is the correct description for Gardasil. Based on this fact, and from this concept, therefore Gardasil cannot be proposed for every woman, because it is costly for the public health funds at this stage. Gardasil might prove to be a useful tool in the long run, after collecting enough data on its administration on girls, and ruling on its safety and effectiveness as well. Until then the Pap screening should be funded and developed for every women in all nations. Finally Pap screening remains the mandatory tools for preventing cervical cancer.

It is still not yet known how much the incidence of cervical cancer in the developing countries is due to the lack of a cervical cytology screening program, and thus many cases are lost without early diagnosis, and that is a big waste, and will contribute to the high mortality rate for a preventable killing disease of women. Therefore it is important to raise the issue with the decision makers, about the importance of Pap testing, in ruling out those affected cases and applying treatment at earlier stages. Gardasil cannot replace the requirement of Pap testing.

Also it is not clear yet if Gardasil will protect against other STDs, plus vaginal and vulvar cancers, and if young men were vaccinated, to cut down the incidence of HPV infection rate, as men are the only reservoir for HPV. Also not known yet is if a booster dose of Gardasil is needed or not as a matter of fact for its effectiveness which will last from 4 to 5 years according to the trials finding.
Lastly it is mandatory to raise public health awareness and education about safe sex, practice, and safety by changing behaviours, and applying a new studied strategy to promote the better reproduction health of the community, by targeting younger age groups with an education mass media campaign which is the cornerstone for any primary health care.

Anonymous, news: In brief, Practice Nurse; 2007; 34, 6; ProQuest Nursing & Allied Health Source, pg. 10

HPV vaccine beyond the hype, 2007, www.ConsumerReports.org 47

Kathie Lynas, Late Clips, Canadian Pharmacists Journal; 2005; 138, 7; ProQuest Nursing & Allied Health Source, pg. 21

Research highlights, www.nature.com/reviews/cancer, 2005, vol 5, p 840.

Drugs and Herbs, Cancer vaccine approved, 2006, Consumer Reports on Health, 6

Monica R McLemore, Gardasil®: Introducing the New Human Papillomavirus Vaccine
Clinical Journal of Oncology Nursing; 2006; 10, 5; ProQuest Medical Library, pg. 559

Barbara Sibbald, News @ a glance, Canadian Medical Association. Journal; 2006; 175, 5; ProQuest Medical Library pg. 464

Nature biotechnology, www.nature.com/naturebiotechnology, 2007, vol 25, no 3

Angie L. Goeser, Quadrivalent HPV Recombinant Vaccine (Gardasil) for the Prevention of Cervical Cancer, steps New Drug Reviews, 2007, American Family Physician, Vol 76, No 4, 574

Anonymous, Merck Gains Approval for Two New Vaccines, Biopharm International; Jul 2006; 19, 7; ProQuest Nursing & Allied Health Source pg. 16

Abby Lippman, Ryan Melnychuk, Carolyn Shimmin, Madeline Boscoe, Human papillomavirus, vaccines and women's health: questions and cautions, 2007, CMAJ, 177(5)

Alicia Priest, Cervical cancer vaccine may come soon to Canada, Canadian Medical Association. Journal; 2006; 175, 3; ProQuest Medical Library pg. 235

Anonymous, New Vaccine Prevents Cervical Cancer, FDA Consumer; 2006; 40, 5; ProQuest Medical Library, pg. 37

Anonymous, CDC releases 2007 immunization schedule, adds 2 new vaccines
Healthcare Traveler; Feb 2007; 14, 8; ProQuest Nursing & Allied Health Source pg. 62

Maryann Napoli, How Vaccine Policy is made: The Story of Merck and Gardasil
HealthFacts; Mar 2007; 32, 3; ProQuest Nursing & Allied Health Source pg. 1

Anonymous, Rapid approval of vaccine for prevention of cervical cancer
WHO Drug Information; 2006; 20, 2; ProQuest Nursing & Allied Health Source pg. 88

Anonymous, Rolling out HPV vaccines worldwide, The Lancet, 2006; 367, 9528; ProQuest Medical Library pg. 2034

Judy Norsigian; Alicia Priest; Robin Barnett, GARDASIL: What you need to know about the HPV vaccine, Canadian Women's Health Network; 2007; 9, 3/4; ProQuest Nursing & Allied Health Source pg. 14

Chemist & Druggist., Clinical News: HPV vaccination for all girls, proquest, 2007. pg. 18

Marc Siegel, Antidote, Medical Marketing and Media; 2006; 41, 8; ProQuest Nursing & Allied Health Source pg. 14

Marc Iskowitz, Gardasil ads remain platonic... for now, Medical Marketing and Media; 2006; 41, 7; ProQuest Nursing & Allied Health Source pg. 11

Cormac sheridan, dublin, biotrin assay to monitor cervical cancer exposure rates, news, vol 25 no, 2007 nature biotechnology

Joanna breitstein, cervical cancer: endangered species, pharmaceutical executive; may 2006; proquest nursing & allied health source, 26, 5 pg.154

Jenny May, HPV vaccination; A paradigm shift in public health, Australian Family Physician, 2007, Vol 36, No 3, 106

Natasha T Metzler, Potential HPV Vaccine Roadblocks, Pharmaceutical Executive; Dec 2005; ProQuest Nursing & Allied Health Source, 25, 12pg. 26

Stella Heley, Pap test update, Australian Family Physician, 2007, vol 36, no 3, 112

Meenakshi Dawar, Shelley Deeks, Simon Dobson, Human papillomavirus vaccines launch a new era in cervical cancer prevention, 2007, CMAJ, 177(5)

Gill Jenkins, HPV vaccine debate, Hospital Doctor; 2007; ProQuest Health Management pg. 38

Pauline Comeau, Debate begins over public funding for HPV vaccine, Canadian Medical Association. Journal; 2007; ProQuest Medical Library; 176, 7, pg. 913