17. The Cervix Flashcards
(105 cards)
1
Q
How is the uterus anatomically divided?
A
The uterus is divided into the corpus (body), isthmus, and cervix.
2
Q
What is the length of the cervix in an adult?
A
The cervix measures 2.5 to 3 cm in length in the adult.
3
Q
What is the typical orientation of the cervix?
A
The cervix is usually angled downwards and backwards.
4
Q
What is the vaginal portion of the cervix called, and how is it structured?
A
The vaginal portion of the cervix is called the portio vaginalis or ectocervix. It is divided into anterior and posterior lips, with the external os in the center.
5
Q
What connects the external os to the uterine cavity?
A
The external os is connected to the uterine cavity by the endocervical canal (endocervix).
6
Q
What is the shape and largest diameter of the endocervical canal?
A
The endocervical canal is an elliptical cavity, measuring 8 mm in its greatest diameter.
7
Q
What is the blood supply to the cervix?
A
The cervix is supplied by the descending branches of the uterine arteries.
8
Q
How does the venous drainage of the cervix occur?
A
The venous drainage parallels the arterial system and communicates with the cervical venous plexus and the neck of the bladder.
9
Q
Where do the lymphatics of the cervix drain?
A
The lymphatics of the cervix drain into two lateral plexuses in the region of the isthmus, which then drain to the external iliac and obturator nodes, the internal iliac nodes, the common iliac nodes, and the sacral nodes.
10
Q
What types of tissue compose the cervix?
A
The cervix is composed of fibrous, muscular, and elastic tissue.
11
Q
What are the two types of epithelium lining the cervix?
A
The cervix is lined by squamous epithelium and columnar epithelium.
12
Q
What is the squamocolumnar junction (SCJ) of the cervix?
A
The SCJ is the border between the stratified squamous epithelium and the mucin-secreting columnar epithelium of the endocervix.
13
Q
What is the original squamocolumnar junction (OSCJ)?
A
The OSCJ is the SCJ where the squamous epithelium meets the columnar epithelium at birth.
14
Q
What is the new or functional squamocolumnar junction?
A
The new SCJ is formed after metaplasia converts columnar epithelium into squamous epithelium. This is the SCJ typically visualized in adult women.
15
Q
What is the transformation zone (TZ) of the cervix?
A
The TZ is the area between the original SCJ and the new SCJ, where metaplasia occurs.
16
Q
What causes the development of the transformation zone?
A
The development of the TZ depends on changes in the length and size of the cervix as the female develops and is exposed to estrogen.
17
Q
What are the two mechanisms by which columnar epithelium is replaced by squamous epithelium?
A
- Direct ingrowth of original squamous epithelium bordering the columnar epithelium.
- Proliferation of undifferentiated subcolumnar reserve cells of the endocervical epithelium that differentiate into squamous epithelium (squamous metaplasia).
18
Q
What is metaplasia?
A
Metaplasia is the physiological conversion of one mature type of epithelium into another equally mature type.
19
Q
When is metaplasia most active in women?
A
Metaplasia is most active during reproductive life and is quiescent in pre-menarchal and post-menopausal women.
20
Q
Why is the transformation zone important?
A
The transformation zone is important because almost all cervical squamous neoplasias and their precursors originate in this area.
21
Q
Where is the transformation zone typically located?
A
In the vast majority of women, the transformation zone is located on the ectocervix.
22
Q
In what percentage of women is the original squamocolumnar junction located on the vagina?
A
In around 4% of women, the OSCJ is located on the vagina.
23
Q
What is the role of cervical cancer screening in cancer prevention?
A
Cervical cancer screening detects precursors to cervical cancer early, allowing for treatment and follow-up to prevent the development of cancer. This is known as secondary prevention
24
Q
Which test is used for cervical cancer screening?
A
Cervical cytology, commonly performed as a Pap smear, is used for cervical cancer screening.
25
What is the target population for cervical cancer screening in the UK?
Women aged 25 to 60 years are the target population for cervical cancer screening in the UK
26
How does the incidence of cervical cancer differ between countries with and without screening programmes?
Countries with no organised screening (e.g., sub-Saharan Africa, Latin America): 40–100 cases per 100,000 women.
Countries with high-coverage screening (e.g., the UK): 5–7 cases per 100,000 women.
Countries with poorer coverage and health services (e.g., the Balkans): 20 cases per 100,000 women.
27
What is the incidence of cervical cancer in the UK with high coverage of screening?
Around 5–7 cases per 100,000 women.
28
What percentage of the target population is covered by the cervical cancer screening programme in the UK?
The UK screening programme covers 87% of the target population.
29
What is the cumulative reduction in cervical cancer with yearly screening?
Yearly screening reduces cervical cancer incidence by 93%.
30
How many Pap smears are performed over a lifetime with yearly screening, and what is the reduction in cervical cancer incidence?
Number of Pap smears: 30.
Cumulative reduction in cervical cancer: 93%.
31
How does the effectiveness of three-yearly screening compare to yearly screening?
Three-yearly screening reduces cervical cancer incidence by 91%, which is only slightly less than the 93% reduction with yearly screening.
Three-yearly screening requires fewer Pap smears (10 vs. 30).
32
What is the cumulative reduction in cervical cancer with five-yearly screening
Five-yearly screening reduces cervical cancer incidence by 84%.
33
How effective is ten-yearly cervical cancer screening?
Ten-yearly screening reduces cervical cancer incidence by 67%.
34
How does the frequency of screening impact the number of Pap smears required?
Yearly screening: 30 Pap smears.
Three-yearly screening: 10 Pap smears.
Five-yearly screening: 6 Pap smears.
Ten-yearly screening: 3 Pap smears.
35
Why is cervical cancer more common in countries with no organised screening programmes?
Lack of screening leads to undetected and untreated cervical cancer precursors, resulting in higher cervical cancer incidence.
36
What is the basis of the South African Cervical Cancer Screening Policy?
Offer asymptomatic women over the age of 30 three free Pap smears in their lifetimes, spaced 10 years apart.
37
What is the difference between a screening Pap smear and a diagnostic Pap smear
Screening Pap smear: Reserved for asymptomatic women as part of a national secondary prevention programme.
Diagnostic Pap smear: Performed in symptomatic women (e.g., abnormal vaginal bleeding, discharge, or pain) as part of a medical work-up.
38
Why does the South African policy focus on screening women over the age of 30?
The yield of disease detection is higher in older women.
Cervical cancer precursors have a long latent period (10–20 years) to progress to cervical cancer.
Screening younger women is less cost-effective as their precursors are often transient with high regression rates, except in HIV-positive immuno-incompetent women.
39
What is the incidence of cervical cancer precursors in HIV-negative and HIV-positive women?
HIV-negative or immuno-competent HIV-positive women: Peak incidence in their early 30s.
HIV-positive immuno-incompetent women: Develop precursors earlier with faster progression to cervical cancer.
40
How effective is infrequent cervical cancer screening?
Screening every 10 years is associated with a two-thirds reduction in the incidence of cervical cancer.
41
Why is the detection of cervical cancer precursors in asymptomatic women not considered a medical emergency?
Cervical cancer precursors have a long latent period (10–20 years).
Asymptomatic women with macroscopically normal cervices require follow-up but not urgent intervention.
42
Why is colposcopy still necessary in asymptomatic women with normal-looking cervices?
Early micro-invasive cancers can develop in a normal-looking cervix.
Colposcopy is performed following specific guidelines to detect such cases.
43
What is the rationale for spacing Pap smears every 10 years in the South African policy?
Even infrequent screening significantly reduces cervical cancer incidence by 67%.
Fewer Pap smears are required for effective prevention, optimizing resources.
44
What is the primary causal event in the development of cervical cancer?
Persistent infection of the cervix with high-risk Human Papillomavirus (HPV) types.
45
How does HPV infection lead to cervical cancer?
Persistent HPV infection causes dysplastic changes in the cervical epithelium.
If untreated, these changes can progress to cervical cancer.
46
What are some terminologies previously used to describe cervical cancer precursors?
Mild, moderate, and severe dysplasia
Mild, moderate, and severe dyskaryosis (used in the UK today)
Cervical intraepithelial neoplasia (CIN) grades 1, 2, and 3
Pap Class I–IV (used in the Netherlands)
47
What is the significance of the Bethesda conference in 1988?
Standardized the terminology for cervical cancer precursors.
Introduced SIL (Squamous Intraepithelial Lesions) terminology for cytological changes.
48
What is the difference between LSIL and HSIL under the Bethesda system?
LSIL (Low-grade SIL):
Includes HPV-related changes and CIN 1 (mild dysplasia).
Often regresses spontaneously, particularly in young women.
Considered a risk factor for cervical cancer.
HSIL (High-grade SIL):
Includes CIN 2 and 3 (moderate to severe dysplasia).
Regarded as a true precursor to cervical cancer.
49
Why was CIN 2 and CIN 3 combined under HSIL?
Difficulty in reliably distinguishing between CIN 2 and CIN 3.
Both are considered true precursors to cervical cancer.
50
Why was LSIL introduced as a separate category?
LSIL reflects early HPV-related changes that often regress spontaneously.
It was considered a marker of increased risk but not an immediate precursor to cancer.
51
Why is standardization of terminology important in cervical cancer screening?
Ensures reliable comparison of studies on natural history and treatment outcomes.
Promotes consistent interpretation of cervical cytology.
52
What is the ASCUS smear, and why was it controversial?
ASCUS (Atypical Squamous Cells of Uncertain Significance): Equivalent to the British term 'borderline abnormality.'
Controversy:
- It led to over-servicing of patients with trivial or unimportant lesions.
- 5–30% of women with ASCUS have undiagnosed HSIL lesions, so it cannot be ignored.
53
What did the Bethesda System change about the reporting of normal results?
Previous terms like ‘within normal limits’ or ‘benign cellular changes’ were replaced with:
"Negative for intraepithelial lesion or malignancy."
54
What are the criteria for a Pap smear to be considered satisfactory for evaluation?
The smear must include:
- 8,000–12,000 well-visualized squamous cells.
- At least 10 well-preserved endocervical or squamous metaplastic cells.
Unsatisfactory criteria:
- If ≥75% of the slide is obscured by blood or inflammatory cells.
55
What was introduced at the 2001 Bethesda conference?
Refinements to the classification system, including clearer guidance on adequacy of Pap smears and terminology changes.
Reinforced the need to comment on smear adequacy and to distinguish between satisfactory and unsatisfactory smears.
56
Why is smear adequacy critical in cervical cancer screening?
Inadequate smears may lead to missed lesions or require repeat testing, delaying diagnosis and increasing costs.
57
How has the concept of ASCUS impacted patient management?
Increased follow-up for patients with ASCUS smears due to the potential risk of underlying HSIL lesions.
58
How has the ASCUS category been subdivided?
ASC-US (Atypical Squamous Cells of Undetermined Significance): Represents trivial changes.
ASC-H (Atypical Squamous Cells – cannot exclude HSIL): Represents potentially more significant changes.
59
Did the Bethesda 2001 workshop change the LSIL or HSIL classifications?
No, the LSIL (Low-Grade Squamous Intraepithelial Lesion) and HSIL (High-Grade Squamous Intraepithelial Lesion) classifications remained unchanged.
60
What challenges do atypical glandular cells (AGC) present in cytology?
It is often unclear whether the cells originate from the endocervix or endometrium.
Management recommendation:
- All AGC cases should be referred for colposcopy.
- If a more serious lesion is suspected, it is classified as:
"Endocervical adenocarcinoma in situ."
61
What is the management approach for AGC cases?
Immediate colposcopy to evaluate and confirm the origin of the atypical cells.
Further investigation may be needed if adenocarcinoma in situ is suspected.
62
Why is it important to distinguish between ASC-US and ASC-H?
To avoid unnecessary intervention for trivial changes (ASC-US) while ensuring close follow-up and management for potentially serious lesions (ASC-H).
63
What makes AGC cases challenging in cytology?
It is often unclear whether the atypical cells originate from the endocervix or the endometrium.
64
What is the recommended management for AGC cases?
1. Referral to colposcopy for all cases of AGC.
2. If a more serious lesion is suspected, classify it as:
"Endocervical adenocarcinoma in situ."
65
Why is colposcopy necessary in AGC cases?
To evaluate the source and significance of the atypical cells.
To detect or rule out serious lesions, including adenocarcinoma in situ.
66
What is the classification for a suspected serious lesion in AGC?
Endocervical adenocarcinoma in situ."
67
What co-factors are associated with an increased risk of cervical cancer?
- Smoking
- Micro-nutrient deficiencies
- Certain genetic abnormalities (currently under research)
68
How do traditional risk factors for cervical cancer relate to HPV infection?
Traditional risk factors such as early sexual intercourse, multiple partners, and early pregnancy are surrogates for HPV infection, which is the primary cause of cervical cancer.
69
How might high parity and long-term oral contraception use affect cervical cancer risk?
High parity: May contribute to the persistence of HPV.
Long-term oral contraception use: Has a limited but independent effect on promoting HPV persistence
70
How does condom use affect HPV transmission?
Condoms reduce the viral load of HPV from male to female but do not provide full protection against transmission between partners.
This is due to the multifocal nature of HPV infection in the genital tract.
71
How is HPV transmitted?
HPV is transmitted via skin-to-skin contact.
72
What is the role of cervical cytology in screening for cervical cancer?
Cervical cytology involves collecting exfoliated cells from the cervix, staining them with the Papanicolaou stain, and examining them under a microscope. It is designed to screen asymptomatic women with a macroscopically normal cervix for precancerous or cancerous changes. A biopsy should be performed instead of a smear if the cervix appears abnormal (e.g., cancer is visible), as smears may be falsely negative in these cases.
73
What is the management for ASC – US (Atypical Squamous Cells of Undetermined Significance)?
Asymptomatic women with a normal cervix: Treat any obvious infections and repeat the smear every 12 months.
If the diagnosis persists after 3 consecutive smears, refer for colposcopy.
74
What is the management for ASC – H (Atypical Squamous Cells, cannot exclude High-grade Squamous Intraepithelial Lesion)?
Refer the patient directly for colposcopy.
75
What is the management for LSIL (Low-grade Squamous Intraepithelial Lesion)?
Repeat the Pap smear on two occasions, 6 – 12 months apart.
If the abnormality persists, refer for colposcopy.
76
What is the management for HSIL (High-grade Squamous Intraepithelial Lesion)?
Refer the patient directly for colposcopy.
77
What is the management for AGC (Atypical Glandular Cells) or Endocervical Adenocarcinoma in situ?
Refer the patient directly for colposcopy.
78
What is the management for squamous or glandular cancer?
Urgent referral for colposcopy is required.
79
What is colposcopy?
Colposcopy is an examination where the cervix is magnified and illuminated after the application of 3-5% acetic acid. It is complementary to cytology and helps to identify and classify abnormal areas on the cervix.
80
What are the key objectives of performing a colposcopy?
During colposcopy, the colposcopist attempts to establish the following information:
- Whether SIL (Squamous Intraepithelial Lesion) is present or not.
- The extent of the lesion, particularly whether the outer and upper limits of the lesion can be identified.
- To exclude the presence of occult microinvasion (early invasive cancer not visible to the naked eye).
81
What criteria must be met for a patient to be deemed suitable for therapeutic intervention for cervical lesions?
A patient is deemed suitable for therapeutic intervention if the following criteria are met:
1. Diagnostic parity: The diagnostic modalities of cytology, colposcopy, and histology obtained from colposcopically directed punch biopsy agree.
2. The entire extent of the abnormal area can be identified.
3. There is no evidence of occult microinvasion of the cervix.
4. The endocervical cells of the cervix are reported as normal on cytology.
5. Colposcopy is available in the context of an abnormal Pap smear.
82
What must be true for the diagnostic modalities to agree for a patient to be considered suitable for therapeutic intervention?
The diagnostic modalities of cytology, colposcopy, and histology obtained from colposcopically directed punch biopsy must agree (be in parity).
83
What must be possible for the extent of the abnormal area for the patient to be suitable for therapeutic intervention?
The entire extent of the abnormal area must be identifiable.
84
What is the significance of occult microinvasion in deciding suitability for therapeutic intervention?
There must be no evidence of occult microinvasion (early invasive cancer not visible to the naked eye) of the cervix.
85
What is required for the endocervical cells in cytology for therapeutic intervention to be considered?
The endocervical cells of the cervix must be reported as normal on cytology.
86
Why is colposcopy an important aspect of therapeutic intervention?
Colposcopy must be available in the context of an abnormal Pap smear to assess the cervix further.
87
What was the most popular form of treatment for SIL in the 1980s?
In the 1980s, the most popular treatment for SIL was CO2 laser ablation of the transformation zone.
88
What procedure replaced CO2 laser ablation in the 1990s for the treatment of SIL?
In the 1990s, LLETZ (Large Loop Excision of the Transformation Zone) replaced CO2 laser ablation.
89
What is the advantage of LLETZ (Large Loop Excision of the Transformation Zone)?
LLETZ is performed under local anaesthesia in an outpatient setting and provides a complete specimen for histological examination of the transformation zone (TZ).
90
What can a pathologist determine from the specimen obtained via LLETZ?
A pathologist can determine:
1. That there is no unsuspected, occult microinvasive disease of the cervix.
2. That the lesion has been completely excised.
91
When is a cone biopsy required before therapy can be safely instituted?
A cone biopsy is required under the following circumstances:
- There is disparity between the diagnostic modalities.
- The entire extent of the lesion cannot be visualised at colposcopy.
- There is colposcopic evidence of occult microinvasion.
- The endocervical cells are reported as abnormal on cytology.
- No colposcopy is available in the face of a persistently abnormal cervical smear.
92
What is the primary difference between LLETZ and cone biopsy?
The primary differences between LLETZ and cone biopsy are:
- Indications: LLETZ is a therapeutic intervention, while a cone biopsy is a diagnostic procedure.
- Amount of tissue removed: LLETZ removes approximately 7-10 mm of tissue, whereas a cone biopsy removes up to 2.5 cm of tissue.
93
What is the recommended follow-up after LLETZ?
After LLETZ, the patient should be followed up:
- Every 6 months in the first year.
- Then annually for at least 5 years, though 10 years is likely a more prudent approach.
94
What are the three HPV vaccines that have been developed, and what do they target?
The three HPV vaccines are:
* Cervarix (GlaxoSmithKline) – Targets types 16 and 18 (bivalent vaccine).
* Gardasil (Merck/MSD) – Targets types 6, 11, 16, and 18 (quadrivalent vaccine).
* Nine-valent vaccine – Targets types 6, 11, 16, 18, and an additional 5 high-risk types: 31, 33, 45, 52, and 58.
95
How are the HPV vaccines administered, and what is the usual dosage schedule?
The vaccines are administered intramuscularly in three doses. However, the FDA has approved a two-dose schedule for the bivalent and quadrivalent vaccines for girls up to age 14 who are HIV negative. This approach is also supported by the World Health Organization.
96
What is the mechanism of action of HPV vaccines, and what are their limitations?
HPV vaccines stimulate the production of neutralising antibodies that prevent HPV infection. They are prophylactic vaccines, meaning they prevent infection but do not treat existing HPV infections. The vaccines are effective only for the types they target and have no impact once a person is already infected with those types.
97
Who should receive the HPV vaccine, and why is it important to administer it early?
The HPV vaccine should be administered to girls aged 9–12 years (before sexual debut). As resources increase, it should also be given to boys. Administering the vaccine early ensures protection before potential exposure to HPV through sexual contact.
98
What evidence supports the efficacy and safety of the HPV vaccines?
There have been numerous high-quality randomized trials showing the vaccines’ efficacy and safety. In Australia, where a national HPV vaccination program using Gardasil is in place, there has been a marked reduction in the incidence of genital warts.
99
What is Liquid Based Cytology (LBC), and how does it work?
Liquid-Based Cytology (LBC) involves taking a smear and immediately placing the spatula into a vial containing a specially prepared preservative solution. The vial is then processed by a robotic machine that can handle over 80 specimens at a time. The machine filters out debris, red and white blood cells, leaving epithelial and glandular cells to be placed on a special slide. The advantage of LBC is that it reduces the percentage of unsatisfactory slides due to obscuring blood and inflammation, making screening easier and faster.
100
What are the benefits of LBC in cervical cancer screening?
Mechanized processing reduces manual labor and improves efficiency.
Lower percentage of unsatisfactory slides due to blood or inflammation.
Easier and quicker slide screening.
Ideal for computerized interpretation, with technology currently being developed for this purpose.
101
What is the role of molecular testing in cervical cancer prevention?
Molecular testing, particularly for high-risk HPV DNA, has been rigorously tested and shows promise in detecting cervical cancer precursors. It involves testing for high-risk HPV types, with Hybrid Capture II (Qiagen) being one of the most studied methods. This test is more sensitive than cytology in identifying high-grade cervical cancer precursors.
102
How does HPV DNA testing compare to conventional cytology in cervical cancer screening?
HPV DNA testing has greater sensitivity than conventional cytology, meaning it is better at detecting high-grade cervical cancer precursors. However, it has a higher false-positive rate (lower specificity) and a lower positive predictive value, which could lead to overtreatment and increased morbidity. Despite this, the higher sensitivity ensures that no lesions are missed.
103
What approach is being taken in some countries to improve cervical cancer screening using HPV DNA testing?
In some countries, HPV DNA testing is used as the primary screening test for women 30 years and older. Women with a positive HPV DNA test then undergo cytology testing. Only if both tests are positive, women are referred for colposcopic assessment. This approach has shown superior test characteristics compared to using cytology alone.
104
What is the ‘screen and treat’ approach for cervical cancer screening in developing countries, and what are its strengths and limitations?
In developing countries, the ‘screen and treat’ approach has been implemented due to limited resources. In this approach, nurses are trained to perform Visual Inspection with Acetic Acid (VIA), where the cervix is washed with 3–5% acetic acid to identify aceto-white lesions. If found, the woman is treated immediately using ablative techniques like cryotherapy or thermocoagulation during the same visit.
Strengths:
- Affordable and implementable in low-resource settings.
- Does not require laboratory infrastructure or skilled interpretation.
- Enables screening and treatment in a single visit.
Limitations:
- When subjected to longitudinal randomized trials, VIA showed poor test characteristics, with lower sensitivity and a high rate of overtreatment.
- However, it remains a valuable tool, better than having no screening program at all.
105
How has HPV DNA testing been incorporated into the ‘screen and treat’ approach in developing countries?
In developing countries, HPV DNA testing has been tested as part of the ‘screen and treat’ approach and has shown significant benefits in reducing cervical cancer precursors. One example is the HPV Xpert (Cepheid) test, a simplified version of the Hybrid Capture II test. This test detects 15 high-risk HPV types, provides results in one hour, and can be performed at the primary care level without the need for specialized laboratory staff. Trials are ongoing to assess its effectiveness as a point-of-care test.
