HPV Caused Cervical Cancer

The causative role of human papillomavirus (HPV) in all cancers of the uterine cervix has

been firmly recognized biologically and epidemiologically. Most cancers of the vagina and

anus are likewise caused by HPV, as are a fraction of cancers of the vulva, penis, and

oropharynx. HPV-16 and -18 account for about 70% of cancers of the cervix, vagina, and

anus and for about 30–40% of cancers of the vulva, penis, and oropharynx. Other cancers

causally linked to HPV are non-melanoma skin cancer and cancer of the conjunctiva.

Although HPV is a necessary cause of cervical cancer, it is not enough cause. Thus, other

cofactors are necessary for development from cervical HPV infection to cancer. Long-term

use of hormonal contraceptives, high parity, tobacco smoking, and co-infection with HIV

have been identified as established cofactors; co-infection with Chlamydia trachomatis (CT)

and herpes simplex virus type-2 (HSV-2), immunosuppression, and certain dietary

deficiencies are other probable cofactors. Genetic and immunological host factors and viral

factors other than type, such as variants of type, viral load and viral integration, are likely to

be important but have not been clearly identified [1].

 

 

Keywords: Uterine cervix, oropharynx, conjunctiva, Chlamydia trachomatis, non-melanoma

skin cancer

 

*Author for Correspondence: Email ID: jaishwa@hotmail.com

 

 

INTRODUCTION

Cervical cancer is the second most

common cancer in women worldwide, and

knowledge regarding its cause and

pathogenesis is expanding rapidly. The

common cause is persistent infection with

one of about 15 genotypes of carcinogenic

human papillomavirus (HPV).

 

There are four major steps in cervical

cancer development: infection of

metaplastic epithelium at the cervical

transformation zone, viral persistence,

progression of persistently infected

epithelium to cervical precancer, and

invasion through the basement membrane

of the epithelium. Infection is extremely

common in young women in their first

decade of sexual activity. Persistent

infections and precancer are recognized,

typically within 5–10 years, from less than

10% of new infections. Invasive cancer

arises over many years, even decades, in a

minority of women with precancer, with a

peak or plateau in risk at about 35–

55 years of age. Each genotype of HPV

acts as an autonomous infection, with

differing carcinogenic risks linked to

evolutionary species. Our understanding

has led to improved prevention and

clinical management strategies, including

improved screening tests and vaccines.

 

The new HPV-oriented model of cervical

carcinogenesis should gradually replace

older morphological models based only on

cytology and histology. If applied wisely,

HPV-related technology can minimise the

incidence of cervical cancer, and the

morbidity and mortality it causes, even in

low-resource settings [1]

.

 

 

 

HPV Caused Cervical Cancer Bathula et al.

__________________________________________________________________________________________

 

IJCBCP (2015) 1–8 © JournalsPub 2015. All Rights Reserved Page 2

THEORY

Cancer

Cancer is a disease in which the body cells

become abnormal and divide without

control. Cancer cells invade nearby tissues

and they may spread through the blood

stream and lymphatic system to other parts

of the body.

 

Definition of HPV

Human papillomavirus (HPV) is a virus

that can be passed from person to person

through skin-to-skin contact.

 

More than 100 types of HPV have been

found. More are harmless, but about 30 of

these types infect the genital areas and you

get them through sexual contact with an

infected partner. Usually the body fights

off HPV before it can cause health

problems, if it is not cleared then they may

lead to either low-risk or high risk factors.

 

Low-risk HPV types (6, 11, 42, 43, and

44) can cause genital warts in both men

and women. These are soft growth on the

skin and mucus membranes of genitals.

They may also be found on the penis,

vulva, urethra, vagina, cervix, and around

and in the anus. Warts are not life

threatening, but can be emotionally hard

for a person to deal with [2]

.

 

High-risk HPV types (16, 18, 31, 33, 39,

45, 51, 52, 56, 58, 59, 66, 68, and 73) can

lead to cancers of cervix, vulva, vagina

and anus in women. In men it leads to

cancers of anus and penis.

 

HPV is a very common virus. It is more

common in young men and women in their

late teens and early 20s. Some researches

suggest that at least three out four people

who have sex will get a genital HPV

infection at some time in their lives.

 

IS HPV MORE COMMON IN

WOMEN OR MEN?

HPV is just as common in men and

women. But HPV is less likely to cause

serious health problems in men. Most men

with HPV never get symptoms or health

problems from it. There is no approved

test for HPV in men. HPV and genital

warts are just as common in native women

as in women of other ethnicities.

 

Cervical cancer is less common in native

women than in African-American and

Hispanic women. But cervical cancer is

more common in native women than in

white women.

 

In United States, about 12,000 women get

cervical or other genital cancers from HPV

every year.

 

And about 7,000 men get head, neck and

anal cancers from HPV every year. HPV

and genital warts are just as common in

native women as in women of other

ethnicities.

 

TRANSMISSION

HPV is primarily spread through vaginal,

anal, or oral sex, but sexual intercourse is

not required for infection to occur. HPV is

spread by skin-to-skin contact. Sexual

contact with an infected partner is the most

common way the virus is spread. Like

many other sexually transmitted diseases,

there often are no signs and symptoms of

genital HPV infection.

 

YOU CANNOT GET HPV FROM

o Toilet seats; o Kissing, hugging, or holding hands; o Being unclean; o Sharing food or utensils, Family

history.

 

WHAT DISEASES DOES HPV

INFECTION CAUSES?

o Approximately 12 types of HPV cause genital warts. These growths may

appear on the outside or inside of the

vagina or on the penis and can spread

to nearby skin. Genital warts also can

grow around the anus, on the vulva, or

on the cervix.

 

 

 

IJCBCP (2015) 1–8 © JournalsPub 2015. All Rights Reserved Page 3

International Journal of Cell Biology and Cellular Processes Vol. 1: Issue 1

www.journalspub.com

 

o Approximately 15 types of HPV are linked to cancer of the anus, cervix,

vulva, vaginal and penis they also can

cause cancer of the head and neck.

These types are known as “high-risk

types” [3]

.

Cervical cancer begins in the women’s

cervix. It is the narrow organ at the bottom

of the uterus that connects to the vagina.

And in the same way it can grow on other

body organs.

 

HOW DOES HPV CAUSES CANCER

OF CARVIX?

The cervix is covered by a thin layer of

tissue made up of cells. If HPV is present,

it may enter these cells. Infected cells may

become abnormal or damaged and begin to

grow differently. The changes in these

cells may progress to what is known as

precancer. Changes in the thin tissue

covering the cervix are called dysplasia or

cervical intraepithelial neoplasia (CIN). In

most women, the immune system destroys

the virus before it causes cancer. But in

some women, HPV is not destroyed by the

immune system and does not go away. In

these cases, HPV can lead to cancer or,

more commonly, precancer [4]

.

 

Types of Cervical Cancer

There are mainly two types of cervical

cancer. They are distinguished by the

appearance of cells under a microscope:

a. Squamous cell carcinoma, b. Adenocarcinoma.

 

Squamous Cell Carcinoma Begin in the thin flat cells that line the

bottom of the cervix. This type of cervical

cancer accounts for 80 to 90 percent of

cervical cancer.

 

Adenocarcinoma Develop in the glandular cells that line the

upper portion of the cervix. These cancers

make up 10 to 20 percent of cervical

cancer.

Sometimes both types of cells are involved

in cervical cancer, other types of cancer

can develop in the cervix, but these are

rare. Like metastatic cervical cancer, they

spread to other parts of body.

 

Symptoms When present, common symptoms of

cervical cancer:

Normally appear in the form of a

cauliflower like growths, may also be flat

they can be found on the inside and the

outside of the vagina. These growths may

take weeks or even an year to show after

having sex with an infected partner [5]

.

 

Vaginal Bleeding This includes bleeding between periods,

after sexual intercourse or postmenopausal

bleeding.

 

Unusual Vaginal Discharge A watery, pink or swelling discharge is

common.

Pelvic Pain Pain during intercourse or at other times

may be a sign of abnormal changes to the

cervix or less serious condition.

 

Signs of Advanced Stages of Cervical

Cancer o Cervical cancer may spread within

the pelvis, to the lymph nodes or

else, where in the body signs of

advanced cervical cancer includes:

o Weight loss, o Back pain, o Leg pain or swelling, o Involuntary, ongoing release of

urine or feces,

o Bone-fracture, o Fatigue[6].

 

Screening Tests for Cervical Cancer

It usually takes years for cervical cancer to

develop. During this time, HPV infection

can cause cells on or around the cervix to

become abnormal which may lead to

cancer.

 

 

HPV Caused Cervical Cancer Bathula et al.

__________________________________________________________________________________________

 

IJCBCP (2015) 1–8 © JournalsPub 2015. All Rights Reserved Page 4

The two cervical cancer screening methods

are:

a. Pap test, b. HPV test.

 

Pap Test (Sometimes called cervical

cytology screening)

o The Pap test is one of the most reliable and effective cancer

screening methods available for

women. It checks for changes on

your cervix so that problems can be

found and removed before they

turn into cancer.

o Here in the Pap test, the health care provider will use a swab to collect

cells from your cervix and check

under a microscope for any

problems.

o Women should start getting Pap tests three years after the first sex,

or by age of 21, whichever comes

first.

o Women should get Pap test at least once every three years.

 

HPV Test

o HPV test may also be used with the Pap test in certain cases. The HPV

test looks for HPV, the virus that

can cause cell changes in the

cervix.

o The HPV test can identify 13–14 of the high-risk types of HPV

[7] .

 

HPV Vaccine against Cervical Cancers

and Genital Warts

The vaccine has been widely tested in girls

and women. It is safe and has no side

effects. The most common side effect is

soreness in the arm.

There are two types of HPV vaccines

namely:

a. Cervarix, b. Gardasil.

 

Cervarix

o It is a 3-dose series. o Only to females.

o Female: 11 or 12 years of age. This age group has the best response to

the vaccine, and the vaccine must

be given before sexual activity

begins. HPV vaccine can be started

at 9 years. It is also recommended

for females aged 13 through

26 years who have not been

vaccinated.

o Prevents most cases of cervical and anal cancer in females if the

vaccine is given before a person is

exposed to HPV.

 

Gardasile

o A series of 3-dose series given for both males and females.

o Female and male: 11 or 12 years of age. This age group has the best

response to vaccine, and the

vaccine must be given before

sexual activity beings. HPV

vaccine started at 9 years. It is

recommended for females aged 13

through 26 years who have not

been vaccinated or did not finish

the 3-shot series.

o It is also recommended for males aged 13 through 21 years who have

not been vaccinated or did not

finish the 3-shot series. It may be

given to males aged 22 through

26 years and should be given to

high-risk males aged 9 through

26 years [8]

.

 

BIOLOGICAL MECHANISMS OF

HPV CARCINOGENESIS

In previous decades, our understanding of

cancer pathways was rudimentary and

often incorrect. In the face of such

uncertainty, arguments based on

assumptions of molecular biology were not

particularly convincing. However, with the

large body of work now available it is

possible to develop a reasonable

understanding of the ways in which cancer

may develop and ways in which HPV

infection can drive the process. Thus, we

can say with some confidence that it is

 

 

 

IJCBCP (2015) 1–8 © JournalsPub 2015. All Rights Reserved Page 5

International Journal of Cell Biology and Cellular Processes Vol. 1: Issue 1

www.journalspub.com

 

plausible for HPV to cause cervical cancer

and, furthermore, we can describe with

reasonable clarity the general steps by

which HPV may do so. Of course there is

a lot of detail still to be revealed, but we

are well on our way to a factual basis for

understanding carcinogenesis rather than

the guesswork and rudimentary models of

just two decades ago.

 

What follows is a description of selected

information that may illuminate salient

aspects of the natural history of HPV and

reasons why a mostly benign infectious

process sometimes results in malignancy.

It must be understood by readers that the

pathways are based on extensive

experimentation in biopsied human tissues,

in tissue culture, and other kinds of

molecular biology systems. However,

many details of pathway modifications and

aberrant pathway effects are speculative;

they have not been shown to occur inside

the relevant precancerous and cancerous

tissues of living hosts. However, despite

the many holes and inconsistencies, the

models are still quite compelling and

cohesive in facts. In future, we expect to

see these molecular models being tested in

human subjects.

 

Essentially all HPV types produce warty

lesions but only high risk types promote

the development of cervical cancer to any

appreciable extent. Such differences

between HPV types may seem surprising,

given the high DNA and structural

similarities. However, a large functional

divergence caused by small genetic

changes is the norm in many biological

systems. Variations in carcinogenic

potential among HPVs are principally

governed by the E6 and E7 proteins;

specifically by the capacities of these

proteins to interact with and alter or

destroy key cell cycle regulatory

molecules.

 

The progress and outcome of an HPV

infection depends on HPV type,

anatomical location, and the nature and

timing of local cellular and tissue

influences. Virions access basal and

parabasal cells in areas of erosion and viral

DNA enters the cell nuclei. Establishment

is tied to the tissue proliferative activity of

epithelial cells and, in the case of

extensive tissue repair; the viral infection

can become widely disseminated.