Cervical Cancer Flashcards

1
Q

Function of the female production system

A
  • Producing eggs
  • Facilitating fertilisation ( process by which sperm cell fuses with an egg to form a zygote initiating the development of a new organism)
  • Supporting Pregnancy
  • Giving Birth
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2
Q

Female Reproductive System main structures and function

A
  • Ovaries: Produce eggs and female sex hormones
  • Fallopian Tubes ( Oviducts): Transport eggs from ovaries to uterus and are the site of fertilisation
  • Uterus (Womb): Holds and nourishes developing fetus during pregnancy
  • Cervix: Connects uterus to vagina and produces mucus to aid sperm movement
  • Vagina: Connects cervix to external genitalia and serves as birth canal
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3
Q

Cervical Anatomy

A
  • Crucial to understanding HPV infection and impact on cervical cancer development
  • Two main parts: ectocervix (exocervix): outer part of cervix visible during gynaecologic exam. Covered in thin, flat cells (squamous cells)
    • Endocervix: inner part of the cervix forming canal connecting vagina to uterus. Covered in column-shaped glandular cells that make mucus.
  • external opening of cervix: external os
  • internal opening into uterus: internal os
  • squamous columnar junction ( transfomation one): border where endo and ectocervix meet
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4
Q

Changes to the cervix during puberty/ pregnancy

A

Before puberty: junction between the squamous and columnar epithelium in the cervix located inside the cervical canal.
During puberty or pregnancy, :The transformation zone: columnar epithelium of the cervix turns outward, exposing it to the acidic environment of the vagina triggering squamous metaplasia, where the columnar cells transform into squamous cells.
this area becomes more susceptible to the development of cervical abnormalities, including precancerous and cancerous changes often linked to HPV infection .

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5
Q

Diagnosis; Cervical Cytology

A

Cytology: detects abnormalities in cervical cells that indicates precancerous or cancerous changes.
- Pap Smear or Cervical Cytology Test, cells are collected from the cervix using a swab and then smeared onto a glass slide or placed in a liquid medium- cells then examined under a microscope by a cytopathologist, who looks for changes in cell morphology, such as enlargement, irregular shape, or increased nuclear-to-cytoplasmic ratio, that may suggest cancerous growth.
- Used for early detection and intervention as part of screening to prevent the progression of cervical cancer and improve patient outcomes.

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6
Q

Diagnosis: Punch and Cone Biopsy vs LLETZ

A
  • Help doctors assess the severity of abnormalities detected in cervical screening and guide further management decisions.
  • Punch biopsy: removal of a small tissue sample from the cervix for microscopic examination,
  • LLETZ (Large Loop Excision of the Transformation Zone): surgical procedure that removes a larger portion of abnormal cervical tissue for both diagnosis and treatment.
  • cone biopsy/ conization: involves the surgical removal of a cone-shaped section of tissue from the cervix for both diagnostic and therapeutic purposes, particularly in cases of cervical dysplasia or early-stage cervical cancer.
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7
Q

TNM staging system for cervical cancer

A
  • describes extent of cancer based on: T (tumor size and invasiveness), N (spread to nearby lymph nodes), and M (metastasis or spread to distant organs).
  • allows doctor to detemine best treatment options/ determine prgoniss/ outxome for patients with cervical cancer
  • Carcinoma in situ: Non-invasive cancer confined to the original site without spreading to surrounding tissues.
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8
Q

What is a multivalent vaccine

A

vaccine that targets multiple strains or types of a pathogen in a single formulation.

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9
Q

Structure and Genome Human Papilloma Virus (HPV)
Function of Genome

A
  • Simple structure: Tiny ball or sphere
  • tough outer shell ( capsid) surrounding its genetic material
  • Genetic Material: Instruction manual for making more virus particles

genome: genetic material
- circular double stranded DNA molecule containing genes
Early genes : E1 to E6: involved in starting infection by helping virus copy itself and take control of cell
Late genes ( L1 and L2) : come into play later to build outer shell of new virus particles

both gene types function co-ordinately to ensure virus can infect cells and reproduce

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10
Q

Viral Life cycle: URR and ORI

A

URR (Upstream Regulatory Region)
ORI ( Origin of Replication)
ensure efficiency replication and propagation of virus within host cells

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11
Q

Mechanism of HPV Infection

A

C- HPV enters cervical cells though epithelial micro-abrasions
- Infects cervical cells integrating its DNA into host genome
- Infects basal epithelial cells and replicates spreading upwards through epithelial layers
-Cell regulation disrupted leading to uncontrolled cell growth and potentially cancerous changes

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12
Q

Role of HPV oncogenes (E6 and E7)

A
  • produced by high-risk HPV strains.
  • E6 targets tumor suppressor protein p53 for degradation, allowing infected cells to evade (escape) apoptosis.
  • E7 binds and inactivates retinoblastoma
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13
Q

HPV and its link to cervical cancer

A
  • Progresses to cervical intraepithelial neoplasia (CIN): characterised by abnormal changes in cervical cells
  • CIN can progress to invasive cervical cancer spreading beyond epithelium and potentially metastasising to other organs if no intervention
  • CIN scale: CIN1 (mild dysplasia), CIN2 (moderate dysplasia), and CIN3 (severe dysplasia and carcinoma in situ).
  • Carcinoma in situ: cancer cells are present but haven’t spread beyond where they started growing.”
  • Dysplasia: abnormal growth or development of cells, tissues, or organs, often indicating precancerous changes.
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14
Q

Immunohistochemistry - CIN detection

A
  • HPV E6/E7 oncoprotens inactivate tumour suppressors P53 & RB: P16 over expressed and can be demonstrated by IHC

Detects and visualises specific proteins in tissue sections using antibodies labelled with a visible marker

P16 immunohistochemical staining in cervical intraepithelial neoplasia (CIN) indicates overexpression of p16 protein, suggestive of HPV-driven cellular changes and increased risk of progression to cervical cancer.
Strong and diffuse staining is characteristic of high-grade CIN lesions.

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15
Q

WHO Cervical Cancer Elimination Strategy

A

-Aims to reduce burden of cervical cancer world wide via comprehensive measures to reduce cervical cancer incidence and mortality rates globally:

  • Vaccination: Promoting HPV vaccination to prevent HPV infection, focusing on reaching ADOLESCENT girls.
  • Screening:, Understanding the scientific principles behind screening involves recognizing the role of HPV infection as the primary cause of cervical cancer and the effectiveness of early detection in preventing disease progression. Implementing evidence-based screening guidelines that balance sensitivity and specificity to maximize detection of high-risk lesions while minimizing unnecessary interventions and healthcare costs. Establishing regular cervical cancer screening programs, such as Pap smears or HPV testing, to detect precancerous lesions and early-stage cancers for timely intervention.
  • Diagnosis and Treatment: Ensuring access to affordable and effective diagnostic tools and treatment options, including cryotherapy, loop electrosurgical excision procedure (LEEP), and surgery, for managing precancerous lesions and early-stage cervical cancer.
  • Palliative Care: Provides specialized support to improve the quality of life for individuals with serious illnesses, focusing on symptom management including pain management and psychosocial support, and holistic well-being.
  • Health Education: Conducting public awareness campaigns to educate communities about the importance of HPV vaccination, regular screening, and early treatment-seeking behavior.
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16
Q

Challenges to the WHO Cervical Cancer Elimination Strategy

A
  • health inequalities in vaccine access and potential HPV transmission from unvaccinated populations are critical considerations.
  • low-resource settings: limited infrastructure, funding, and trained healthcare personnel may hinder the availability and accessibility of screening services, exacerbating health inequalities.
  • cultural beliefs, social stigma, and lack of awareness about cervical cancer and HPV vaccination may further contribute to disparities in screening uptake and vaccination rates.
  • movement of populations and the globalization of travel increase the risk of transmission of HPV strains between countries, potentially introducing new high-risk strains into populations with low vaccination coverage.
  • highlights the importance of international collaboration and coordination in HPV vaccination efforts and surveillance programs to address emerging viral variants and prevent the spread of infection.
17
Q

HPV types and associated diseases

A
  • diverse group of viruses infecting epithelial cells of skin and mucous membranes
  • illustrate diverse range of HPV types and associated diseases- highlight HPV vaccination importance for prevention of HPV-related cancer and other issues
18
Q

HPV infection types targeted for vaccination

A
  • Cervarix vaccine for HPV types 16 and 18 ( causing cancer)
    Gardasil: HPV types 6,11 ( cause genital warts), HPV 16 AND 18 (cause cancer)
  • Gardasil 9 vaccine: HPV types 16,18,,31,33,45,52,58 ( cancer causing) and HPV types 6,11 ( cause warts)
    recommended for adolescents as its most effective prior to exposure to the virus
19
Q

How HPV Vaccination Shields Against HPV Vaccinations

A
  • vaccines contain harmless fragments of HPV proteins triggering an immune response in the body without causing disease
  • immune system produces antibodies that can recognise and fight off HPV infections in encountered in the future
  • involves activation of B cells that produce antibodies and T cells that help coordinate immune response
  • antibodies produces B cells that bind to specific proteins on the virus preventing it from infecting cells and aiding in its immune cell destruction
  • vaccination harnesses principles of immunology to train the immune syste, whilst helping to mitigate risks associated with antigenic drift/shift/viral emergence
20
Q

What are antigenic drift, shift and viral emergence?
- Evolutionary HPV risks and role of vaccinations

A
  • Antigenic drift : small changes in the viral proteins over time, which may affect the effectiveness of the antibodies produced by the immune system. Vaccination can still provide some level of protection against drifted strains, as the immune system may still recognize and respond to common features shared among different strains.
  • Antigenic shift: (an abrupt, major change in a flu A virus, resulting in new HA and/or new HA and NA proteins in flu viruses that infect humans.) more significant change that can result in the emergence of entirely new strains of the virus. Vaccination helps mitigate the risk of antigenic shift by reducing the overall prevalence of the virus in the population, thereby decreasing the likelihood of new strains emerging.
  • Viral emergence occurs when new strains of the virus arise and begin spreading in the population.
  • Vaccination plays a crucial role in preventing viral emergence by reducing the number of susceptible individuals who can become infected and contribute to the spread of the virus. Additionally, vaccination helps limit the opportunities for the virus to undergo genetic changes that could lead to the emergence of new strains
21
Q

Maintaining Viral Efficacy

A
  • Population monitoring for viral shift drift essential for vaccine efficacy
  • Detection of new high-risk HPV strains informs updates to vaccination programs and screening strategies requiring ongoing surveillance and research to adapt screening protocols and vaccination efforts to effectively address evolving HPV-related health challenges and optimise patient outcomes
  • HPV vaccines provide long-lasting protection against HPV infection and cervical cancre creating herd immunity protecting those who are not vaccinated thus lowering cervical cancer cases in the community
22
Q

HPV negative cancers risk factors vs HPV positive cancers

A

HPV positive:
- Higher incidence
- Younger age
- Earlier Stage
Squamous cell carcinomas
- Less Lymph node metastasis
- Better Prognosis

HPV negative:
- Lower incidence
- Old age
- Advanced stage
- Adenocarcinoma
- More lymph node metastasis
- Worse Prognosis

23
Q

HPV-negative cancers suspected pathogenesis

A
  • Needs more research
    • may arise from alternative pathways of carcinogenesis, independent of HPV infection. HPV-negative cervical cancer research and progress has been overshadowed by progress for HPV-positive cervical cancer.
  • Gaps in knowledge regarding biologic characteristics, biomarkers, classification, models, and therapeutic targets
  • . About ONLY 1.5% of medical publications on cervical cancer address HPV-negative disease.
  • HPV-negative cervical cancers are considered immunologically cold and unresponsive to immunotherapies. Must be further investigated to identify molecular aetiologies that could serve as future therapeutic targets.
24
Q

Consideration of whether HPV negative cancers truly lack HPV or caused by unknown subtypes

A
  • Ongoing debate
  • Certain HPV types may not be detectable with current testing methods, leading to false negative factors

Other factors may contribute to development of cervical cancer in the absence of detectable HPV infection
- genetic mutations
-hormonal influences
- Environmental Exposures

25
Q

Ethical Considerations Surrounding Screening for HPV negative cancers

A
  • may require difference approaches; Alternative Biomarkers/Imaging Techniques
  • concerns about trade-off between sensitivity and specificity in screening programs as well as allocation of limited healthcare resources

ethical conidiations: ensuring Equitable access to screening and Addressing potential disparities in health care delivery

26
Q

Graphs illustrating trends and statistics of cervical cancer incidence and screening outcomes

A
  • prevalence of high-risk HPV types 16 and 18 reduced with increasing number of women vaccinated in England
  • studies shown protection against HPV lasts at least 10 years
  • p-value trend of less than .001 considered good as it indicates a significant result suggesting that the observed trend or relationship is unlikely due to random chance.
  • provides strong evidence to support the hypothesis being tested in the study.