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9. CP - Diseases of the Reproductive System > (46) Diseases of the reproductive system 1 > Flashcards

(46) Diseases of the reproductive system 1 Flashcards

1
Q

What does VIN stand for?

A

Vulval intraepithelial neoplasia

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2
Q

What does CIN stand for?

A

Cervical intraepithelial neoplasia

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3
Q

What does CGIN stand for?

A

Cervical glandular intraepithelial neoplasia

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4
Q

What does VaIN stand for?

A

Vaginal intraepithelial neoplasia

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5
Q

What does AIN?

A

Anal intraepithelial neoplasia

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6
Q

What is dysplasia?

A

The earliest morphological manifestation of multistage process of neoplasia

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7
Q

What are the benefits of recognising dysplasia?

A

The cells show cytological features of malignancy but no invasion (in-situ disease)

no invasion = no metastasis = curable

Gives chance to treat potentially fatal tumour before it arises

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8
Q

What may happen if a dysplasia is left untreated?

A

Significant chance of developing invasive malignancy

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9
Q

Describe the main structural features of the human papilloma viruses (HPVs)

A
  • double stranded DNA virus
  • 7.9kb circular genome
  • 7 ‘early genes’
  • 2 ‘late’ genes
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10
Q

How many different types of HPV is there?

A

Over 100 subtypes, based on DNA sequence

Different types affect different tissues and cause different things

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11
Q

Is HPV common or rare?

A

Common - in most women, HPV will not cause long term harm and will be cleared by the immune system in most cases

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12
Q

How are HPVs divided/classified?

A

Into low and high oncogenic risk

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13
Q

What are low risk HPVs associated with?

A

Genital warts and other low-grade cytological abnormalities

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14
Q

What are the most common low risk HPVs?

A

HPV 6 and 11

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15
Q

What are high risk HPVs associated with?

A

High-grade pre-invasive and invasive disease

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16
Q

What are the most common high risk HPVs?

A

HPV 16 and 18

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17
Q

What proportion of cervical cancers contain HPV DNA?

A

99.7% of cervical cancers contain HPV DNA

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18
Q

Which types of HPV cause most cervical cancers?

A

Types 16 and 18 are associated with 70% of cervical cancers

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19
Q

What do low risk HPV 6 and 11 cause?

A

Lower genital tract warts (condylomas = benign squamous neoplasms), low grade INs (intraepithelial neoplasias)
- vary rarely in malignant lesions

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20
Q

What do high risk HPV 16, 18, 31 and 33 cause?

A

High grade intraepithelial neoplasia (IN) and invasive carcinomas

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21
Q

Why is the cervix painted with acetic acid in diagnostics?

A

Abnormal epithelium becomes ‘acetowhite’ (appears white when you put acetic acid on it) - colposcopist can recognise the pattern of acetowhite which has a high risk of being due to CIN

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22
Q

The Gardasil (Merck) vaccine protect against which HPV types?

A

6, 11, 16, 18

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23
Q

The Cervarix (MSK) vaccine protects against which HPV types?

A

16, 18

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24
Q

How has the UK HPV vaccination programme changed?

A
  • began in sept 2008
  • started with cervarix
  • age 12-13 with catch up up to 18
  • switch to gardasil in sept 2012
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25
Q

What are HPV early genes involved in?

A
  • early genes are expressed at onset of infection
  • they control viral replication
  • in oncogenic viruses, they are involved in cell transformation
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26
Q

What do HPV late genes code for?

A

Capsid proteins

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27
Q

High risk HPVs integrate into host chromosomes and do what?

A

Upregulates E6 and E7 expression (E6 and E7 = early genes)

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28
Q

High risk HPVs cause up regulation of E6 and E7 (early genes). What does E6 do?

A

Binds to and inactivates p53 - this leads to accumulation of genetic damage

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29
Q

What is the role of p53?

A

‘guardian of the genome’ - p53 mediated apoptosis in response to DNA damage

Therefore, inactivation by E6 leads to accumulation of genetic damage

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30
Q

High risk HPVs cause up regulation of E6 and E7 (early genes). What does E7 do?

A

Binds to RB1 gene product - this leads to dysregulation of cell proliferation

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31
Q

What is the role of RB1?

A

It is a tumour suppress gene - it controls the G1/S checkpoint in the cell cycle

Therefore, binding of E7 to the RB1 gene product leads to dysregulation of the cell cycle/ cell proliferation

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32
Q

What are the 2 types of vulval intraepithelial neoplasia (VIN)?

A
  • classical/warty/baseloid VIN

- differentiated VIN

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33
Q

Which type of VIN is related to HPV infection?

A

Classical/warty/baseloid is related to HPV infection

Differentiated VIN is not HPV-related

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34
Q

Who do the 2 different types of VIN affect?

A

Classical = younger people

Differentiated (non-HPV related) = older people

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35
Q

How is classical VIN graded?

A

Graded VIN 1-3

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36
Q

How is differentiated VIN graded?

A

Not graded

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37
Q

Which conditions does differentiated VIN tend to occur in?

A

Chronic dermatoses especially lichen sclerosus

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38
Q

State the main features of classical/warty/baseloid VIN

A
  • graded VIN 1-3
  • related to HPV infection
  • younger people
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39
Q

State the main features of differentiated VIN

A
  • not graded
  • not HPV related
  • occurs in chronic dermatoses especially lichen sclerosus
  • older people
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40
Q

How often does VIN recur?

A

35-50% recur

Positive margins predict recurrence

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41
Q

How often does VIN progress to invasive carcinoma?

A

Progression to invasive carcinoma in 4-7% of treated women and up to 87% of those untreated

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42
Q

Progression of VIN to become invasive is most likely to occur in whom?

A

Those who are post-menopausal or immunocompromised (as HPV is not contained by the immune system)

43
Q

Spontaneous regression of VIN may occur, particular in whom?

A

Particularly in young, postpartum women

44
Q

The most common vulval cancer (90%) is what type?

A

Squamous cell carcinoma

45
Q

Describe the different oncogenic pathways leading to squamous cell carcinoma of the vulva

A
  • associated with VIN

- associated with inflammatory dermatoses

46
Q

Symptomatic lichen sclerosus carries what risk?

A

15% risk of malignancy

47
Q

Vulval squamous cell carcinoma may be associated with what?

A

VIN or inflammatory dermatoses

48
Q

Describe the typical predictable spread of vulval squamous cell carcinoma

A
  • locally to involve vagina and distal urethra
  • to ipsilateral inguinal lymph nodes
  • to contralateral inguinal lymph nodes
  • to deep iliofemoral lymph nodes (25% if inguinal lymph nodes +ve)
49
Q

How does the depth of invasion of vulval squamous cell carcinoma relate to risk of lymph node metastasis?

A

less than 1mm depth of invasion = very rare lymph node mets

1-3mm = 10%

more than 4mm = 40%

50
Q

What procedure would be done if after wide local excision, the depth of invasion of VSCC was found to be over 1mm?

A

Lymph node sampling (groin node dissection or sentinel node biopsy)

51
Q

What staging system is used to stage gynaecological cancers including vulval squamous cell carcinoma?

A

FIGO staging system

52
Q

What is the prognosis in vulval squamous cell carcinoma?

A 
5 year survival
stage I = 95%
stage II = 90%
stage III = 70%
stage IVA = 20%
stage IVB = less than 10%
53
Q

Rather than vulval squamous cell carcinomas, 5% of vulval tumours are what?

A

Malignant melanomas (easy to recognise when pigmented, aggressive tumours)

54
Q

What is the mean age of vulval malignant melanoma patients?

A

50-60

55
Q

How common is local recurrence of vulval malignant melanoma?

A

1/3 of cases

56
Q

Spread of vulval malignant melanoma to where is frequent?

A

Spread to the urethra is frequent

Lymph node/haematogenous spread is common

57
Q

The depth of invasion (Breslow depth) of vulval malignant melanoma correlates with what?

A

Lymph node (LN) involvement

58
Q

Rarely, a malignant melanoma has no pigment at all. What is this called?

A

Amelanotic melanoma

59
Q

What makes up the other 5% of vulval tumours? (other than squamous cell carcinoma and malignant melanoma)

A

Paget’s disease (extra-mammary Paget’s disease)

60
Q

What is the mean age of vulval Paget’s disease patients?

A

80

61
Q

What sort of appearance do you get in vulval Paget’s disease?

A

Pruritis/burning/eczematous patch (may be eczema but Paget’s should be in differential diagnosis and biopsy should be considered)

62
Q

What type of cancer is vulval Paget’s disease?

A

In-situ adenocarcinoma of squamous mucosa - tends to recur following excision

Can develop invasive adenocarcinoma

63
Q

Paget’s disease of the vulval may be related to which carcinoma?

A

Low rectal carcinoma (where there is prominent perianal component)

Also bladder and cervix

64
Q

Is there an underlying tumour in extramammary Paget’s disease?

A

Usually no underlying tumour

Whereas in Paget’s disease of the nipple, there is underlying ductal carcinoma in-situ spreading into the epidermis)

65
Q

What is the transformation zone of the cervix?

A

A physiological area of squamous metaplasia in the cervix (where columnar cell lining becomes squamous cell lining)

66
Q

When does the transformation zone develop?

A

After menarche

67
Q

Why is the transformation zone an important area?

A

The TZ is vulnerable to the effects of HPV - it is the site of development of CIN

68
Q

Is the squamous mucosa of the cervix ectocervical or endocervical?

A

squamous = ectocervical

columnar = endocervical (more inside)

69
Q

Which type of mucosa of the cervix is more red in colour?

A

Columnar (endocervical) is more red in colour

Squamous/ectocervical is more pale

70
Q

What happens to the location of the TZ post-menopause and what are the consequences?

A

It retracts up the canal, might not be seen colposcopically and might be difficult to sample cyologically. Might not be able to excise CIN easily with LLETZ - so diagnosing and treating CIN post-menopause is problematic

71
Q

Where in the cervix is the squamocolumnar junction located?

A

At the external os

72
Q

Which area is sampled in a cervical cytology sample?

A

The transformation zone

73
Q

What is cervical intraepithelial neoplasia (CIN)?

A

The pre-inavsive stage of cervical squamous cell carcinoma (SCC)

74
Q

What does the cervical screening programme aim to detect?

A

Cervical intraepithelial neoplasia (CIN)

75
Q

What is CIN graded according to?

A

Increasing abnormality

76
Q

How is CIN graded?

A

CIN I, II, and III

CIN I = low grade

CIN II and III = high grade

77
Q

What is the chance of regression in the 3 grades of CIN?

A

I = 60%

II = 40%

III = 33%

78
Q

What is the chance of persistence in the 3 grades of CIN?

A

I = 30%

II = 40%

III = 56%

79
Q

What is the chance that CIN I will progress to CIN III?

A

10%

80
Q

What is the chance that CIN I will progress to invasion?

A

1%

81
Q

What is the chance that CIN II will progress to CIN III?

A

20%

82
Q

What is the chance that CIN II will progress to invasion?

A

5%

83
Q

What is the chance that CIN III will progress to invasion?

A

20-70%

84
Q

What is the first management of CIN I?

A

Just watch and wait as there is a high chance of regression

High grade ones are treated as there is a significant risk of progression and invasion

85
Q

What are the features that make the cervical screening programme a good test?

A
  • high sensitivity and specificity
  • test is not harmful
  • there is a defined pre-invasive stage (CIN)
  • natural history is long enough to allow intervention
  • simple, successful treatment for pre-inasive stage
86
Q

Is the cervical screening programme a test for cancer?

A

No! It is a test for the pre-invasive stage, not cancer (the test is not good at detecting invasive cancer)

87
Q

How does the cervical screening programme affect rate of cervical cancers?

A
  • regular attendance prevents 90% of cancers

- rate would be 50% higher without screening

88
Q

At what ages is cervical screening done?

A

25 = first invitation

25-49 = 3 yearly

50-64 = 5 yearly

65+ = only screen those who have not been screening since age 50 or have had recent abnormal tests

89
Q

What technique does the cervical screening programme use?

A

Uses liquid-based cytology (sample with brush, brush goes into liquid medium, liquid goes to cytology)

Focused high risk HPV testing

90
Q

Why is there no cervical screening below the age of 25?

A
  • evidence does not support its use
  • reactive changes in young people produce confusing cytology
  • unnecessary LLETZ procedures can have obstetric consequences
91
Q

What is done if cervical screening shows borderline nuclear change/low grade dyskaryosis?

A

HPV testing (and then colposcopy +Rx is HPV comes back positive)

92
Q

What is done if cervical screening shows high grade dyskaryosis/invasive malignancy?

A

Refer for colposcopy + Rx

93
Q

In colposcopy, the cervix is often painted with what and why?

A

Acetic acid, to highlight potentially abnormal epithelium

94
Q

What does LLETZ stand for?

A

Large loop excision of the transformation zone

95
Q

What is the main surgical treatment for CIN?

A

LLETZ (as the transformation zone is where CIN happens)

96
Q

What is the most important causative factor of cervical squamous cell carcinoma?

A

High risk HPV

97
Q

Other than HPV, what are the other risk factors for cervical squamous cell carcinoma?

A
  • multiple sexual partners
  • male partner with multiple partners
  • young age at first intercourse
  • high parity
  • low socioeconomic group
  • SMOKING
  • immunosuppression
98
Q

What may be some clinical presentation features of an ulcerated cervical carcinoma?

A
  • bleeding
  • discharge
  • signs of local spread eg. hydronephrosis, and urinary symptoms
99
Q

At what age groups is cervical squamous cell carcinoma most common?

A

25-39

100
Q

Name another type of cervical cancer (other than cervical SCC)

A

Cervical adenocarcinoma

101
Q

What are the features of cervical adenocarcinoma?

A
  • presentation/spread is the same as SCC
  • related to high risk HPV
  • precursor is cervical glandular intraepithelial neoplasia (CGIN)
  • treated the same as CIN/CSCC
102
Q

What is the precursor to cervical adenocarcinoma?

A

Cervical glandular intraepithelial neoplasia (CGIN)

103
Q

Why is the stage for stage prognosis worse for cervical adenocarcinoma than for cervical squamous cell carcinoma?

A

Due to radioresistance

104
Q

What is used to cure many cervical adenocarcinomas?

A

LLETZ

some require more radical surgery eg. lymph nodes dissection, and some chemotherapy and radiotherapy

9. CP - Diseases of the Reproductive System (5 decks)

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