Development of cancer occurs from continuous unregulated proliferation of abnormal cells in
any part of the body. Generally, cell division takes place for a limited span of time. A network
of signals coordinate together to indicate when a cell can divide and also check for errors that
can be fixed. But, abnormality in the nodes of this network can trigger cancer where the normal
cells develop, divide and redivide instead of undergoing apoptosis, and form new abnormal cells.
The abnormalities accumulated in multiple cell regulatory systems result in loss of growth control
that reflects on several aspects of cell behavior, differentiating cancer cell from normal cells.
These cancer cells invade other parts of the body via blood circulation or lymph vessels and spread
throughout the body (metastasis). Several factors contribute to cancer such as tobacco smoking,
genetic predisposition, etc. Generally, normal cells possess the ability to help repair the DNA that
is damaged, but in cancer cells, the damaged DNA is not repaired. This increases the risk of inheriting
the damaged DNA from the parents to the offspring accounting for inherited cancer. Cancer usually
forms solid tumors except a few such as leukemia (blood cancer). Not all abnormal cells are cancerous-benign
tumors which are not life-threatening and do not metastasize, can be removed surgically from the
body. Malignant cells can invade and metastasize and are referred as cancerous cells.
Most important mechanism of cancer featured are
1. Impairment of DNA repair pathway
2. Transformation of normal gene to an oncogene
3. Malfunction of tumor suppressor gene
CLASSIFICATION OF CANCERS
Tumors (benign and malignant) are classified according to the type of cell from where they originate.
Some of the categories are carcinomas, sarcomas, leukemias and lymphomas. Carcinoma are
malignancies of epithelial cells. Sarcoma are rare solid tumors of connective tissues which includes
muscles, bone, cartilage, and fibrous tissues. Leukemias and lymphomas are malignancies arising
from the blood-forming cells and cells of the immune system. Tumors are also termed according to
the cell type involved in tissue of origin such as lung or breast carcinomas; fibrosarcomas develop
from fibroblasts, and erythroid leukemias from erythrocytes (Red blood cells). Some of the most
common types of cancer encountered are breast, prostate, lung, and colon/rectal cancer.
CANCER SCREENING
Screening for cancer is undertaken to reduce mortality by early detection and treatment of cancer.
Cancer screening consists of primary and secondary prevention strategies. Preventing the occurrence
of cancer is primary prevention while secondary prevention deals with early diagnosis of cancer
through screening that aims in detecting abnormal cells before they develop into cancer, ultimately
improving the health outcomes.
Screening is said to be the initial step towards early delection of cancer or premalignant conditions in
individuals lacking signs and symptoms. Early detection benefits the patient in increasing the chances
of survival by allowing initiation of early treatment of the cancer and reducing or inhibiting its metastasis
and subsequent complications. There are two prerequisites for cancer screening, firstly, screening should
minimize the diagnosing time in cases that are highly probable to cause death. Secondly, early treatment
should help prevent over-treatment after the onset of clinical presentation.
? Principles for Efficient Screening of Cancer
For effective screening of cancer following points must be considered,
1. Burden of Suffering
Effectiveness of cancer screening is based on the frequency of cancer in a population and its
consequences on health. If the prevalence rate determines that the probability of the cancer
to arise in an individual from the screened population is lower then larger number of tests are
to be performed to detect even a single case of cancer. This is because most of the positive test
result may have greater chances of the result being erroneous (a false-positive result).
2. Accuracy and Reliability of the Cancer Detecting Screening Test
Secondary consideration of the cancer screening test is to determine whether the available tests
can detect cancer at its earliest with minimal false-positive result and falsenegative results.
Greatest concern of the test also includes three main parameters such as sensitivity, specificity
and predictive value. Reliability and reproducibility are other crucial parameters that indicate
that the same results should be obtained if the screening test is repeated multiple times
under the same conditions.
3. Effectiveness of Early Detection
Screening for cancer is not justified if treatments are unavailable for a particular form of cancer.
Even availability of effective treatment may not be enough, since, in spite of using the best
treatment regimens, most cancers progress in such a way that they are difficult to stop or treat.
For such cancers early screening tests are introduced to improve the outcome of early institution
of treatment. If there are no incremental health benefits for those who are diagnosed early as
compared to those who are diagnosed after signs and symptoms and do not fare equal in health
status, then screening is not considered effective. Effectiveness is not fruitful until early diagnosis
helps reduce morbidity after treatment or allow the patient to live a longer life.
Some of the commonly screened cancers are.
? Cervical Carcinoma
It is the second most common type of cancer manifested in women worldwide. This cancer is more
prevalent in women living in low and middle income countries. The peak age for developing cervical
carcinoma is 55-59 years." It is caused by Human Papilomaviruses (HPV) that are the members of the
family of Papovaviridae. HPV is a non-enveloped virus whose transmission occurs primarily by skin-to-skin
contact. HPV infects the basal cells of stratified squamous epithelium. HPV replication cycle begins
by the virus entering the epithelium through mild abrasion (damage due to scraping away) of the epidermis
layer. Once inside the host cell, HPV activates DNA replication that can progress to the surface of the
epithelium. Viral replication is considered non productive in the basal layer therefore, the virus establishes
itself at a low copy number to produce its own DNA. Subsequently, the virus switches to rolling circle mode
of DNA replication where the DNA is amplified to high copy number, producing capsid proteins and causes
viral assembly.
Screening Techniques
Screening tests for cervical cancer are HPV testing and Pap Smear or Pap Test
1. HPV Testing
Previously, molecular HPV "reflex testing was conducted to assess the need of colposcopy in women
with typical squamous cells of undetermined significance. Co-testing (Pap cytology and HPV testing)
is more sensitive in comparison to cytology testing alone in detecting the rare adenocarcinomas of the
cervix. Later, HPV test was approved as the primary screening method that is highly reliable, similar to
co-testing. HPV testing is utilized as primary screening and its further continuation is recommended for
detecting cellular changes that can initiate new screening guidelines on cancer prevention. HPV
vaccination programs providing HPV testing may also offer a cost-effective strategy to monitor long-term
efficacy of vaccination.
In this technique, a brush is inserted into the endocervix (opening of the uterus) to remove a small
part of the tissue which is placed in a tube containing transport media and sent to the laboratory
for further investigations.
2. Papanicolaou (PAP) Testing
Annual Pap test is considered by the leading groups of gynaecologists as recommendable for yearly
Pap testing. This blood tests is used to detect abnormal cells in the vagina and cervix. Routine screening
test helps in the detection of precancerous cells and can help prevent the development of cervical
cancer. It also reveals the presence of infection and inflammation in the cervical and vaginal areas.
Pap test involves sampling cells that are collected from the cervical area. In liquid-based methods,
a spatula or a brush is used to obtain sample and is placed into a liquid preservative and sent to
laboratory. In the laboratory, examination of the sample is carried out by cell suspension followed
by processing of the sample on the slide, staining and examination of the cells under microscope.
? Colorectal Carcinoma
Colorectal cancer (CRC) is the most common cancer that arises from benign neoplasms called tubular
adenomas and serrated polyps. CRC is formed when acquired genetic and epigenetic changes that
mutate the normal grandular epithelial cells into invasive and adenocarcinomas are accumulated.
The polyp to cancer progression sequence involves a step that initiates the formation of benign
neoplasms- adenomas and serrated polyps, which after several changes, have the potential to
progress to invasive adenocarcinoma. Serrated polyps along with sessile serrated adenomas/polyps
(SSA/P) and the traditional serrated adenomas (TSA) also possess the potential for turning malignant.
In general population, screening can detect and remove the polyps before they undergo malignant
transformation.
Screening Techniques
1. Colonoscopy
This screening test examines the entire colon and rectum with the help of flexible fiber optic endoscope.
This flexible colonoscope is inserted into the rectum and the entire colon is screened for polyps.
This screening detects for asymptomatic cancers and also helps in removing the precancerous lesions.
2. Computed Tomographic Colonography (CTC)
CTC also called as virtual colonoscopy is a computerized tomography examination of the abdomen
and pelvis in which the imaging information is processed with a special imaging software that
provides a picture of rectum and colon. For this technique, bowel preparation and colonic insufflation
is required but not conscious sedation that is generally required for colonoscopy.
? Fibrosarcoma
The World Health Organization has defined adult fibrosarcoma as a malignant neoplasm or tumor
that is made of fibroblasts with variable collagen production. It is a rare, highly malignant soft tissue
sarcoma of mesenchymal cells originating from transformed spindle shaped fibroblasts. They are
mostly located either in deep soft tissue or adjacent to bones. This cancer was considered to be
the most common adult sarcoma, although over the past few decades, the incidence of adult
fibrosarcoma has dramatically decreased.
This was possible due to reasons such as
1. Evolution in the categorization of soft tissue tumors
2. Recognition of fibrosarcoma and characterizing them under clinically, morphologically,
and under genetically distinctive subtypes
3. Understanding the mesenchymal and non mesenchymal tumors that may mimic fibrosarcoma
Screening Techniques
For most cancers, particularly those that belong to the group sarcomas, surgery is critical for cure.
Detection of soft tissue tumors require cytogenetic and molecular techniques that look out for the
tumor type-specific genetic alterations. Individual with a strong family history of sarcoma possessing
certain inherited conditions caused by mutant tumor suppressor gene have increased risk of
developing soft tissue sarcomas. This mutated gene can be detected by genetic testing and can
be divided into two major genetic groups
1) Sarcoma with specific genetic alterations and simple karyotypes such as reciprocal chromosomal
translocation and specific oncogenic mutations
2) Sarcoma with non-specific genetic alterations and complex unbalanced karyotypes
Genetic abnormalities including chromosomal numerical changes, translocations, gene amplifications
are detected by cytogenetic techniques such as karyotyping, Fluorescence in situ Hybridization (FISH),
while other small deletions, insertions or point mutations require molecular genetic techniques such
as polymerase chain reaction (PCR) and sequence analysis.
? Breast Cancer
Breast cancer is characterized by the proliferation of malignant cells in the breast tissue after undergoing
several epithelial changes in the terminal ductal lobular unit. Tumors primarily occur in the ducts (tubes
that carry milk to the nipple) and secondarily in the lobules (glands that produce milk). Cell composition
of stroma in the ducts includes various leukocytes, fibroblasts, myoepithelial cells, etc. This myoepithelial
cells are epigenetically altered in carcinoma in situ. Therefore, myoepithelial cell number decreases and
the release of basement membrane degrading enzymes resulting in invasive carcinoma. Several factors
such as age, genetics, family history, endocrine factors are implicated in its pathogenesis. Germ-line
mutations in genes such as BRCA1 (mapped to chromosome 17921), BRCA2 (mapped to chromosome
13q12.3), p53 and PTEN increase the risk of developing hereditary cancer in an individual. These genes
are few among the other high to moderate penetrance breast cancer susceptibility genes. Each breast
cancer case has its own characteristics, depending on its sensitivity to hormones, over expression of
certain proteins, etc.
Screening Technique
1. Mammogram
Early treatment of breast cancer is based on the detection of non-palpable masses at its earliest.
Mammogram screening is an examination of breast by X-ray based procedure to patients with or
without signs and symptoms of breast cancer. Its benefit is that small tumors may be effectively
detected and subsequently treated with less aggressive regimens and save lives. Mammogram
is known for its sensitivity, specificity, positive predictive values, non-invasiveness, costeffectiveness
and remains as the gold standard screening technique.
Significant growth in knowledge about cancer biology has led to great progress in early detection
of cancer, and its treatment and prevention in recent years. Cancer research is progressing by
focusing more on antiangiogenic chemotherapy, nanotechnology based diagnosis, RNA expression
profiling and proteomics, etc. Efforts to eradicate human cancer are now focused on new cancer
treatment methods and drug targets. More clinical trials to cure cancer are encouraged for better
life ahead and standing tall in the fight against Cancer.
