Carcinogens and infectious pathogens

Question 1

describe the HPV viruses

Answer 1

HPV is classified into different types based on its genetic material. types 1,2,3,4 cause benign conditions like warts. These can affect areas such as the cervix, vulva, vagina, penis, anus, and throat, tonsils 6-11. the infection can persist and lead to the development of cancers, by high-risk genotypes like HPV 16 and 18.
HPV can spread through direct skin-to-skin contact, sexual activity, and in rare cases, vertical transmission during childbirth. Some types of HPV also spread through contaminated surfaces or fomites (direct ). Most people with HPV do not have symptoms, which is why it can be spread unknowingly. Vaccines are available to help prevent infection with the most common high-risk and low-risk HPV types.

Question 2

How does the hpv16 cause cancer

Answer 2

1. Infection of Epithelial Cells: HPV16 infects the epithelial cells,. In the case of HPV16, it typically affects the mucosal surfaces (such as the cervix, anus, and throat).
2. Viral Integration into Host DNA: HPV16 contains two key proteins—E6 and E7—which play a significant role in the development of cancer. These viral proteins can integrate into the host cell’s DNA.
   Disruption of Tumor Suppressor Proteins:
3. E6 Protein: The E6 protein produced by HPV16 binds to and degrades p53, a crucial tumor suppressor protein. p53 normally helps repair DNA damage or triggers cell death (apoptosis) in cells with irreparable damage. By inactivating p53, the virus prevents the cell from undergoing apoptosis, allowing abnormal or damaged cells to survive and divide.
   E7 Protein: The E7 protein binds to and inactivates (Rb) protein, another tumor suppressor. This leads to the uncontrolled progression of the cell cycle, promoting cell division even when the DNA is damaged.
4. Uncontrolled Cell Growth: By disabling the tumor-suppressing functions of p53 and Rb, HPV16 allows infected cells to evade normal growth control mechanisms, leading to abnormal cell proliferation.
5. Accumulation of Genetic Mutations: Over time, the uncontrolled cell division can result in the accumulation of additional mutations in the host cell’s DNA. This can cause the cells to become cancerous.
6. Cervical and Other Cancers: HPV16 is responsible for around 66-70% of cervical cancers, and it is also linked to other cancers, including anal, penile, vulvar, vaginal, and oropharyngeal cancers.

Question 3

What is the treatment and/or management of hpv

Answer 3

for warts : topical treatments, cyrotherpay, surgical removal,
for cancer related : Regular Screening: For cervical cancer, regular screening with Pap smears, Colposcopy and Biopsy
For Warts: Treatments are aimed at removing warts, such as cryotherapy, topical treatments, or surgery.
For Cancer: Early detection and treatment are crucial, involving surgery, radiation, chemotherapy, and immunotherapy. Regular screening helps catch precancerous changes early.
Prevention: HPV vaccines (Gardasil, Cervarix) can prevent many HPV infections, particularly those that cause cancer.

Question 4

1. Review the mechanisms by which viruses can drive carcinogenesis.

Answer 4

Oncogene Activation
Examples:
HPV: High-risk HPV types, such as HPV16 and HPV18, produce proteins (E6 and E7) that inactivate tumor suppressors like p53 and Rb (retinoblastoma protein), leading to uncontrolled cell division.
Human Herpesvirus 8 (HHV-8): This virus contains genes that can activate cellular pathways that encourage cell survival and proliferation, which can lead to the development of Kaposi’s sarcoma.
Inactivation of Tumor Suppressor Proteins
Tumor suppressor proteins include p53, Rb, and p16, which regulate the cell cycle and apoptosis.
Examples:
HPV: The E6 protein of high-risk HPV binds to p53 and promotes its degradation, preventing the cell from undergoing apoptosis (programmed cell death) in response to DNA damage.
Hepatitis B virus (HBV): HBV can affect p53 and Rb activity, contributing to liver cancer.
Chronic Inflammation
Chronic inflammation leads to the continuous activation of immune cells, production of cytokines, and oxidative stress, all of which can damage DNA, promote cell survival, and create mutations that drive cancer.
Examples:
Hepatitis C virus (HCV): Chronic HCV infection leads to liver inflammation and fibrosis, which can progress to liver cancer (hepatocellular carcinoma) over time.
Human Immunodeficiency Virus (HIV): Chronic HIV infection can lead to persistent immune activation and inflammation, contributing to various cancers, including Kaposi’s sarcoma and non-Hodgkin lymphoma.