CERVICAL CANCER A CURSE FOR GROWING AGE WOMEN: (A REVIEW)

About Author:
Shambhavi Singh
M.pharma, Singhania University
Jhunjhunu, Rajasthan
Shambhavisingh6777@gmail.com

Abstract
Based on the figures from the World Health Organization, more than 20 lakhs women die worldwide because of cervical cancer per year. Cervical cancer, a potentially preventable disease, found as the second most common malignancy in women worldwide. In India, the disease accounts for a probable 24 percent of  India’s cancer cases among women and in addition to that 74,000 Indian women die annually from the disease, which results from the unusual growth of cells in the cervix. Cervical cancer is the most frequent disorder among women age near about 50 that increased the death rate  in  Indian rural women as compared urban due to lack awareness and don’t gain proper education. Cancer causing growth in the cervix is not a solitary type. It is not usually linked with hereditary genetic factor but a number of variable factors (Chemical, environmental and biological) indirectly enhance the risk of cervical cancer by increasing the possibility that a woman can contact an HPV infection. National Cancer Control Program emphasizes the significance of early detection and treatment. But our country has no well thought-out screening program and many women in India lack information regarding the disease and way to prevention and treatment facilities. Therefore, it is most of important to treat properly cervical cancer and make awareness in Indian women regarding its treatment and proper management.

REFERENCE ID: PHARMATUTOR-ART-1895

Introduction
Awareness towards the etiologic role of human papillomavirus (HPV) infection in cervical cancer result in advice of adding HPV testing to the screening regimen in women 30-64 years of age. Anyhow, women who have developed symptoms and abnormal screening test found, or a bulky lesion of the cervix are best looked over with colposcopy and biopsy.
Treatment of cervical cancer may vary with the different stages of the disease. For early invasive stages of cancer, surgery is the treatment of choice. For further foster cases, radiation therapy along with chemotherapy is the current standard of treatment.

What is cervix?
The cervix is the lower third portion of the uterus that forms the neck of the uterus and opens into the vagina which is also called the endocervical canal. The opening of the cervix is called the os. The cervical os dilates during menstrual flow. However, when pregnancy is gained the cervical os closes to help keep the fetus in the uterus till birth. Some other important function of the cervix occurs during child birth when the cervixes widen to allow the child to pass through the uterus to the vagina.

The cervix is outlined by the epithelium that is made of a thin layer of cells. Epithelial cells can be either squamous or columnar. Squamous cells are flat and scaly, similar to that of the vagina, apart from it are smooth and lacks rete pegs while columnar cells appear, as indicated by name, column-like. Usually cervical cancer develop slowly beside thatmost of cancer are squamous cell carcinomas, emerging in the squamous epithelial cells that line the cervix. Second most common type is adenocarcinoma, arising from glandular epithelial cells. Very few cases of cancer are observed in other type of cells in cervix.

HPV
HPV is a group of small DNA viruses that are commonly found in 70 – 80% of peoples before they reach 50. Luckily most of the cases do not cause cancer. In  near about 90% cases our body’s immune system kill HPV naturally within 1-2 years.

Unfortunately, sometime the virus survives in women for years. If it happens so for 15-20 years, then it can convert normal cell to cancerous cell. Approx 100+  types of  HPV have been identified. All these differ minutely from each other in their genetic structure. 20-30 types cause infection exclusively to the lower genital tract.

Not all HPVs can be treated equal .
The genital HPV types can be divided into two categories: low risk HPVs and high risk HPVs also known as oncogenic or carcinogenic on (on basis of their capability towards association and lack of association).

                                Classification of HPV Types by Oncogenic Risk

Low-risk HPV types are actually never found as cancer causative agent therefore also known as non – carcinogenic HPV. High- risk HPV types have been identified as causative agent of the cervix, vagina, vulva, anus, and penis. The most common types HPV detected (≥ 90%) responsible in genital warts are HPV 6 and HPV 11.The commonly found HPV both in normal as well as women with cancer is HPV 16. Mainly 4 HPVs types (16, 18, 31 and 45) cause major of cervical cancer (80%).

Genetic susceptibility
Genetic susceptibility to cervical cancer has been identified via several studies on twins and first-degree relatives, as well as genome-wide linkage studies. Women with first degree biologic relative have two times more risk of developing cervical cancer correlated to women with no biologic first-degree relative with cervical cancer. Less than 1% cases of cervical cancer founded inherited.

Respectively, inheritance happens occasionally. In some studies it is found that cervical cancer can be passed as a part of a syndrome. Peutz-Jeghers syndrome represents one such example. People with this syndrome develop colored spots on skin, lips , hands and feet. These peoples also posses many being growth along their intestine, colon and stomach. The growth may become cancerous with time.

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Every so often these bumps can be viewed in woman’s cervix. If these bumps turn cancerous, than it would be a case of inheritance of cervical cancer. Because it develop of  her Peutz-Jeghers syndrome.

Cancer is induced by change in the DNA of our genome. If the change take place and oncogene form, then it may led to develop cancer. These change can be caused by biological, chemical, neuticinal or environmental factors. Sometimes our cells develop oncogene itself on accident. This can happens during replication or division. Fortunately our cells have ways to protect against DNA damage. And if unable to repair then cell damage to itself  (apoptosis).This apoptosis helps cells to prevent from multiplying and possibly leading to cancer.

Prevent these damaged cells from apoptosis some form of E6 and E7. So that these cells keep building up mutations until they grow indefinitely and leads to development of cancerous cells.

Only two HPV genes, E6 and E7, matter for causing cervical cancer.

Therefore E6 and E7 have to be working for long period. It takes years for mutation in DNA and to build up. And if ever do E6 and E7 stop working, the apoptosis can take place and cancer averts. Luckily most forms of E6 and E7 suicide machinery turns back. Only high risk of HPV has the risky form of E6 and E7.

Pathophysiology
On pathophysiology of cervical cancer immense study has been done in recent years. Molecular analysis has make out that the etiology of cervical cancer in old age women is same as to young age women.

Human papillomavirus  act as a vector that render sensitivity to neoplastic conversion or that can directly influence  transformation to a malignant phenotype in infected epithelial cells.

On study it is found that only 5% of HPV infection results in the up growth of cervical intraepithelial neoplasia (CIN) grade 2 and 3(on the basis of increasing severity of the lesion) within 3 year of infection. Apart 20% of CIN 3 lesion develop to invasive cervical cancer within 5 years, besides only 40% of CIN 3 lesions result to invasive cervical cancer in 30years.

As seen as, only a very small proportion of HPV infection develops to cancer, other aspects must be responsible in the evolution of carcinogenesis. The following factors have been found to influence the progress of CIN 3 lesion.

· Longer use of oral contraceptive enhances the risk of cervical cancer.
· Host immune compromise, poor nutrition condition.
· Absence of routine cytology screening.
· Having multiple sex partners

Etiology
In rare cases, cervical cancer results from genital infection with presence of HPV, that is known as human carcinogen. However HPV infection can be transferred via non sexual route, although in major cases result from sexual contact. Consequently majority risk factors found are as follows:
·         Sex at much younger age.
·         Having multiple sex partners.
·         History of sexually transferred diseases.

Epidemiologic
Epidemiological study shows that the incidence varies in various part of the country of cervical cancer. Highest risk of cervical cancer has been found in Asian women.Cervical cancer is reported as the second most widespread cause of cancer causing deaths in women in developing countries however is not even amongst the top 10 causes in developed countries.In Indian women, cervical cancer is the most frequent and killer disease with 226, 000 new cases registered and 80, 000 death taking place each year.

In the United States, cervical cancer is comparatively uncommon. The incidence of death causing cervical cancer has declined gradually in the US over the past few years; since 2004, rates have get down by 2.1% per year in women less than 50 years of  age and by 3.1% per year in women older than 50 years. This leaning has been credited to mass screening with Pap tests. Cervical cancer rates go on rising in several developing countries, on the other hand.

Patient Education
Cervical cancer is overrepresented among middle class women and minority in India. It is essential to increase awareness about the advantage of Pap test screening for prevention of cervical cancer among women. Instructing about the benefit of HPV vaccination is also important but must be modified by the information that vaccination cannot be altered form regular screening.

The best way to promote women to undergo cervical screening involved invitations. That may take any of the following forms:
·         Appointments
·         Phone calls
·         Letters
·         Verbal recommendations
·         Prompts
·         Summarize letters

Prevention
A vaccine well known as Gardasil has been developed that prevents against the two high-risk HPV types (types 16 and 18), that cause 70% of cervical cancers in women. It moreover prevents against two low-risk HPV types (types 6 and 11), that cause 90% of genital warts.  

An additional vaccine called Cervarix is accessible, which prevents against the similar two high-risk HPV types (types 16 and 18). It does not prevent against low-risk HPV types that cause genital warts. Some doctors may propose this vaccine rather than Gardasil.

Over 65 million vaccines of Gardasil have been given safely, in more than 100 countries around the world.

Diagnosis
Human papillomavirus infection must be present for cervical cancer to occur. Whole estimation starts with Papanicolaou (Pap) testing.

Screening recommendations
According to the new guidelines, issued by ACOG the majority women do not need cervical cancer screening more frequently than every 3-5 years.

Present screening recommendations for precise patient age groups are as follows :
· < 21 years: No screening preferred
· 21-29 years: Pap smear after every 3 years
· 30-65 years: HPV and cytology co-testing after every 5 years is preferred.
· >65 years: No screening suggested if prior screening has been negative and high risk is not found.

Management
HPV infection can be prevented by HPV vaccines. The following 2 HPV vaccines are approved by the FDA:
· Gardasil (Merck): This vaccine is approved for girls & women of 9-26 years age to avoid cervical cancer caused by HPV types 6, 11, 16, and 18; it is also permitted for males 9-26 years of age.
· Cervarix (GlaxoSmithKline): This bivalent vaccine is approved for girls and women of 9-25 years age to avoid cervical cancer caused by HPV types 16 and 18.

The Advisory Committee on Immunization Practices (ACIP) suggestion for vaccination are as follows:
· Scheduled vaccination of females aged 11-12 years of age with 3 doses of any HPV2 or HPV4
· Scheduled vaccination with HPV4 for boys aged 11-12 years of age, besides males aged 13-21 years of age who have not been vaccinated earlier.
·  Vaccination with HPV4 in males aged 9-26 years of age for avoidance of genital warts; scheduled use not recommended.

REFERENCES
1.    Mulcahy N. Bevacizumab Extends Survival in Advanced Cervical Cancer. Available at medscape.com/viewarticle/779002.
2.    Rinki Verma “The Unknown Mystery of Death - Risk Factor for Development of Cancer CERVIX in Indian Women.”Available at pharmatutor.org/articles/the-unknown-mystery-of-death-risk-factor-for-development-of-cancer-cervix-in-indian-women
3.    Broder J. Pap tests less frequent under new guidelines. Available at medscape.com/viewarticle/773282.
4.    American College of Obstetricians and Gynecologists. Screening for cervical cancer.
5.    [Guideline] Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer.
6.    Debbie Barragan Is cervical cancer hereditary? Available at genetics.thetech.org/ask/ask359
7.    U.S. Preventive Services Task Force. Screening for Cervical Cancer. AHRQ: Agency for Healthcare Research and Quality. Available at uspreventiveservicestaskforce.org/uspstf/uspscerv.htm.
8.    Muñoz N, Kjaer SK, Sigurdsson K, Iversen OE, Hernandez-Avila M, Wheeler CM. Impact of human papillomavirus (HPV)-6/11/16/18 vaccine on all HPV-associated genital diseases in young women.
9.    Gardasil. U.S. Food and Drug Administration. Available at fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM094042. Accessed February 28, 2012.

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