**1. Introduction**

The discovery of HPV (human papillomavirus) was awarded by Nobel Prize. Since 2008, when Prof. Dr. Harald zur Hausen (German Cancer Research Centre, Heidelberg, Germany) found the relationship between HPV and cervical cancer, the debate on HPV and its vaccine never ended (**Figure 1**).

### **Figure 1.**

*HPV and cervical cancer (the Nobel Prize in Physiology or Medicine 2008).*

There are more than 200 known types of HPV and 35–40 types are responsible for anogenital diseases. Fifteen high-risk types were also related to cancer. In order of their level of connection to cancer, the HPV types are: 16, 18, 45, 31, 33, 52, 58, 35, 59, 56, 51, 39, 68, 73, and 82. Out of those, 16 and 18 are responsible for 71–80% of the cancers and are five times more oncogenic than the other 13 types. From the low-risk types, 6 and 11 are responsible for 90% of the anogenital wart [1].

Looking geographically, 16, 18, 45, 31, 33, 52, and 58 are the seven most prevalent types, with little variation between locations [1]. In Turkey, Usubütün et al. found that types 16 and 18 had 76% prevalence in cervical cancers. The first six types (16, 18, 45, 31, 33, and 52) are responsible for 90.6% of the cancers [2].

In **Figure 2**, the full structure of both early (E) and late (L) proteins of HPV are shown, as well as their functions.

**Figure 2.** *L and E proteins of HPV and their functions.*

In their lifetime, women have 80–85% chance to have an HPV infection, which means it is a widespread sexually transmitted disease. Speaking of sexually transmitted, 99% of all types are transmitted via sex, and using condoms do not protect from it (although some studies show that it protects up to 60%, theoretically any contact between testicals and the vulva is enough for transmission); it can spread even if a finger that had contact with the infected organ touches the opposite gender's genetelia (less than 0.1% of all cases), and since the virus requires body heat; it cannot be transmitted via pools, toilets, baths, saunas, or any other non-living surface.

So is HPV a cervical cancer factor, and are there other HPV-related diseases? HPV-related diseases are: cervix, anus, vulva, penis, oropharynx, and oral cavity cancers. The main reason for cervical cancer is HPV. In other words, cervical cancer cannot happen without HPV. HPV is also related to other diseases to some extent (**Figure 3**).

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**Figure 4.**

*England and Wales).*

*HPV Vaccines: Myths and Facts*

*DOI: http://dx.doi.org/10.5772/intechopen.90442*

Recently, its association with lung cancer has been shown. In a study by Xiong

Apart from cancer, anogenital wart is one of the most important social problems. As seen in **Figure 4** for England and the Wales, anogenital wart increases with

In Turkey, anogenital wart prevalence was found as 154/100,000 and in another study that was adjusted for age, point prevalence (lifetime incidence rate) was 3.8% for the full group, and 2.4% for the pregnant population. Prevalence study revealed

The question, then, arises: Is HPV only for females? What about HPV in males? HPV has been shown to be associated with anogenital wart, anal and penile cancers

*Prevalence of anogenital wart in England and the Wales throughout the years (Health Protection Agency of* 

et al. in 17 countries with 6890 cases and 7474 control groups, squamous cell carcinoma, adenocarcinoma and small-cell carcinoma types showed an increase post-HPV infection (Total OR 3.64 (95% CI: 2.60–5.08) for HPV 16: 3.14 (95% CI:

similar results of recurrence with USA and Europe by 15–37% [5, 6].

2.07–4.76) for HPV 18: 2.25 (95% CI: 1.49–3.40)) [4].

a country's level of development.

*HPV-related cancers and their HPV prevalence [3].*

in men [7, 8].

**Figure 3.**

*HPV Vaccines: Myths and Facts DOI: http://dx.doi.org/10.5772/intechopen.90442*

**Figure 3.**

*Human Papillomavirus*

tal wart [1].

shown, as well as their functions.

There are more than 200 known types of HPV and 35–40 types are responsible for anogenital diseases. Fifteen high-risk types were also related to cancer. In order of their level of connection to cancer, the HPV types are: 16, 18, 45, 31, 33, 52, 58, 35, 59, 56, 51, 39, 68, 73, and 82. Out of those, 16 and 18 are responsible for 71–80% of the cancers and are five times more oncogenic than the other 13 types. From the low-risk types, 6 and 11 are responsible for 90% of the anogeni-

Looking geographically, 16, 18, 45, 31, 33, 52, and 58 are the seven most prevalent types, with little variation between locations [1]. In Turkey, Usubütün et al. found that types 16 and 18 had 76% prevalence in cervical cancers. The first six types (16, 18, 45, 31, 33, and 52) are responsible for 90.6% of the cancers [2].

In **Figure 2**, the full structure of both early (E) and late (L) proteins of HPV are

In their lifetime, women have 80–85% chance to have an HPV infection, which means it is a widespread sexually transmitted disease. Speaking of sexually transmitted, 99% of all types are transmitted via sex, and using condoms do not protect from it (although some studies show that it protects up to 60%, theoretically any contact between testicals and the vulva is enough for transmission); it can spread even if a finger that had contact with the infected organ touches the opposite gender's genetelia (less than 0.1% of all cases), and since the virus requires body heat; it cannot be transmitted via pools, toilets, baths, saunas, or

So is HPV a cervical cancer factor, and are there other HPV-related diseases? HPV-related diseases are: cervix, anus, vulva, penis, oropharynx, and oral cavity cancers. The main reason for cervical cancer is HPV. In other words, cervical cancer cannot happen without HPV. HPV is also related to other diseases to some

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**Figure 2.**

any other non-living surface.

*L and E proteins of HPV and their functions.*

extent (**Figure 3**).

*HPV-related cancers and their HPV prevalence [3].*

Recently, its association with lung cancer has been shown. In a study by Xiong et al. in 17 countries with 6890 cases and 7474 control groups, squamous cell carcinoma, adenocarcinoma and small-cell carcinoma types showed an increase post-HPV infection (Total OR 3.64 (95% CI: 2.60–5.08) for HPV 16: 3.14 (95% CI: 2.07–4.76) for HPV 18: 2.25 (95% CI: 1.49–3.40)) [4].

Apart from cancer, anogenital wart is one of the most important social problems. As seen in **Figure 4** for England and the Wales, anogenital wart increases with a country's level of development.

In Turkey, anogenital wart prevalence was found as 154/100,000 and in another study that was adjusted for age, point prevalence (lifetime incidence rate) was 3.8% for the full group, and 2.4% for the pregnant population. Prevalence study revealed similar results of recurrence with USA and Europe by 15–37% [5, 6].

The question, then, arises: Is HPV only for females? What about HPV in males? HPV has been shown to be associated with anogenital wart, anal and penile cancers in men [7, 8].

**Figure 4.**

*Prevalence of anogenital wart in England and the Wales throughout the years (Health Protection Agency of England and Wales).*

Males are the carriers of this sexual-transmitted disease; however, the disease burden is mostly present in females.

So, is there any vaccine developed against this infectious disease, can this disease be eliminated?

First ever vaccination study was developed as a monovalent (for a single type) against 16 with a 100% protection rate [9]. This vaccine was not commercialized.

A bivalent (for 2-types) vaccine against the most cancer-linked types 16 and 18 based on the previous study, as well as a quadrivalent (for four-types) vaccine based on recombinant virus-like particle (VLPs) were developed by the world-leader companies GSK and MSD [10, 11]. Then, a nonavalent (for nine-types) vaccine was developed and commercialized in order to protect against even more cancer-linked HPV types [12].

Since anogenital warts are one of the substantial social problems, it has not been available and bivalent vaccine against HPV 6 and 11 is still in progress. The current vaccines in use do not provide protection against HPV types associated with nonwart anogenital warts and non-melanoma skin cancers (NMSC). Therefore, vaccination studies against L2 proteins are in progress in the phase of animal experiments.

The International Papillomavirus Society, in an excerpt in the Guardian, pointed to Australia as a model for eradicating cervical cancer; they discussed results in between 2005 and 2015 and showed vaccination rates at 78.6% for girls below the age of 15 and 72.9% for boys below the age of 15, since 2016 [13].

World Health Organization (WHO) has developed a strategy plan to eliminate cervical cancer. According to the strategy, to provide a total elimination from cervical cancer, up to 15 years of age 90% of the girls should be vaccinated, 70% of females aged between 35 and 45 should be screened via high sensitivity tests and 90% of women should be successfully treated of cervical diseases (precancerous lesions and invasive cancers). World Health Organization stated that if these goals are reached by 2030, the elimination of cervical cancer would be possible in 2090 (**Figure 5**) (https://www.who.int/docs/defaultsource/documents/cervical-cancerelimination-draft-strategy.pdf?sfvrsn=380979d6\_4).

In Turkey, however, the situation is highly controversial. As of the last months of 2019, nonavalent is not licensed let alone being included in a vaccination programme. Unfortunately, two of our worst examples for vaccination; polio and hepatitis B; shows a 17-year delay in adapting vaccination programs behind the rest of the world. In 1955, there were statements on Milliyet Journal's columns such as

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**3. Facts**

*HPV Vaccines: Myths and Facts*

the levels drop.

of Turkey.

**2. Myths**

*DOI: http://dx.doi.org/10.5772/intechopen.90442*

"The discovery of Polio vaccine caused a stir in Turkey" and "The news of Polio caused an excitement in our country but Turkish practitioners do not want to make any statement before getting informed from authorities." Seventeen years after these statements, polio was eliminated to be included in the vaccination programme

• Vaccinated children never experience HPV infection and never have HPV

• Antibody levels in blood are quite important; the protection loses its effect if

• Herd immunity (protection of the unvaccinated population) does not exist.

• Vaccinated young girls have higher rates of sexually transmitted diseases since

• Autoimmune diseases such as primary ovarian deficiency and Guillain-Barre

• If there is total protection against types in vaccinations, then cancer prevalence

HPV slithers through the cervical cracks and reaches basal cells in about 30 minutes and enters the cells to infect them. Since it does not stay in the vascular system, the antibody response does not form. Inside the cell, DNA is located episomally at first. Episomally located DNA causes a temporary infection and gets excreted with the cell when the cell is visible on the surface. If the DNA of the HPV gets integrated into the cell DNA, persistent infection will occur and some of them advance to

• There is cross-protection so vaccinations of HPV 16 and 18 are sufficient.

• Vaccines are not cost-effective, protected patients are not worth the cost.

• Vaccines are not safe, there are deaths associated with the vaccine.

**3.1 Natural infection protects so there is no need for vaccination**

• Smear or other HPV tests should be performed before the vaccination.

• If a pregnancy occurs during vaccination, it should be terminated.

• Natural infection protects so there is no need for vaccination.

• Vaccinations are not effective when done at later ages.

associated cancer throughout their lives.

• Vaccination cures their related disease.

they feel more sexually comfortable.

of other types will increase.

have higher rates among the vaccinated girls.

**Figure 5.** *Timeline for eliminating cervical cancer.*

### *HPV Vaccines: Myths and Facts DOI: http://dx.doi.org/10.5772/intechopen.90442*

"The discovery of Polio vaccine caused a stir in Turkey" and "The news of Polio caused an excitement in our country but Turkish practitioners do not want to make any statement before getting informed from authorities." Seventeen years after these statements, polio was eliminated to be included in the vaccination programme of Turkey.
