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Flashcards in Cervical cancer Deck (29)
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1

What percentage of women will be infected with HPV in their lifetime?

% of cervical ca due to HPV?

70%

- 99.7%

2

Which strains of HPV cause:
1. Cervical cancer and high grade abnormalities
2. Genital warts and low grade abnormalities

1. HPV 16 & 18 (80% cervical ca and 50% high grade change)
2. HPV 6 & 11 (>90% warts, 10% low grade change)

3

Other cancers associated with HPV

Vulval, vaginal
Oropharyngeal
Penile cancer
Anal cancer

4

HPV virology

Double stranded DNA
Genome enclosed in protein capsule
Major capsid protein from L1 gene is on the outer surface- vaccine creates immune response to this

- early (E) genes and late (L) genes
- E genes conduct its replication and life cycle
- L genes used later in the piece to complete new virus particles
- E genes are in the lower layers and L genes in more superficial layers
- Low risk serotypes 6 and 11 cause genital warts
- Serotypes 16 and 18 cause neoplasia (+ 45 and 31)

Transmission
- penetrative intercourse
- oral and digital also possible
- congenital possible

5

LLETZ

Indication: excision of CIN

Need to orientate specimen

6

Cone biopsy

Indication: Glandular lesions, can't see all of CIN, discrepancy between smear and colp findings, unreliable pt, incomplete LLETZ

7

Investigations for cervical ca

Colposcopy and biopsy
Cone biopsy
EUA +/- cystoscopy + PR +/- sigmoidoscopy
CXR- for distant spread to lungs
CT/MRI/PET scan - not part of formal FIGO staging but can help with surgical planning

8

Investigations for cervical ca

Colposcopy and biopsy
Cone biopsy
EUA +/- cystoscopy + PR +/- sigmoidoscopy
CXR- for distant spread to lungs
Intravenous pyelogram

CT/MRI/PET scan - not part of formal FIGO staging but can help with surgical planning.

9

FIGO staging cervical ca - Stage 2

The carcinoma invades beyond the uterus, but has not extended onto the lower third of the vagina or to the pelvic wall

IIA Involvement limited to the upper two‐thirds of the vagina without parametrial involvement
○IIA1 Invasive carcinoma <4 cm in greatest dimension
○IIA2 Invasive carcinoma ≥4 cm in greatest dimension
IIB With parametrial involvement but not up to the pelvic wall

10

FIGO staging cervical ca - Stage 3

The carcinoma involves the lower third of the vagina and/or extends to the pelvic wall and/or causes hydronephrosis or non‐functioning kidney and/or involves pelvic and/or paraaortic lymph nodesc

IIIA Carcinoma involves the lower third of the vagina, with no extension to the pelvic wall
IIIB Extension to the pelvic wall and/or hydronephrosis or non‐functioning kidney (unless known to be due to another cause)
IIIC Involvement of pelvic and/or paraaortic lymph nodes, irrespective of tumor size and extent (with r and p notations)c
○IIIC1 Pelvic lymph node metastasis only
○IIIC2 Paraaortic lymph node metastasis

11

FIGO staging cervical ca - Stage 4

The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allotted to stage IV

IVA Spread of the growth to adjacent organs
IVB Spread to distant organs

12

Treatment for cervical ca:
- 1a-1b1
- 1b2-3b
- 4

- 1a-1b1: Surgery
- 1b2-3b: Chemoradiation
- 4: individualised

13

Treatment for cervical ca:
- 1a-1b1
- 1b2-3b
- 4

- 1a-1b1: Surgery
- 1a1- if wanting to preserve fertility- cone biopsy only. If family complete- hysterectomy without LN dissection.
- 1b1: Perform radical hysterectomy and pelvic lymphadenectomy if fertility is not required. If fertility is desired, perform a radical trachelectomy and pelvic lymphadenectomy.
- 1b2: tumour is >4cm diameter. The optimal management of women with primary tumours measuring 4cm or more in diameter is controversial. Proposed treatment strategies include: primary chemoradiation with the option of subsequent completion hysterectomy (currently the most used option); neoadjuvant chemotherapy, followed by radical hysterectomy and pelvic radiation, pending pathology findings; primary radical hysterectomy and lymphadenectomy followed by tailored chemoradiation.

Stage 2A: tumour extends onto upper vagina. If cervical tumour is small, in other words <4cm, consider surgical option as above or chemoradiation

Stage 2B-3b: Chemoradiation

Women with locally advanced cervical squamous cell cancer are best treated with primary chemoradiation, as surgery alone will not provide adequate clearance and will still require adjuvant radiation. It is desirable to minimise side effects to avoid dual radical treatments if possible (in other words, surgery plus chemoradiation). Patients are still potentially curable up to stage IVA (up to 15 per cent five-year survival)

- 4: individualised

14

CIN1

Low grade abnormality - conservative follow up with repeat smear in 12 months

15

High grade abnormality- CIN2 or 3

High-grade pre-invasive changes (CIN2 to 3) are treated via diathermy (wire loop excision), laser or cryotherapy. Single treatment is usually extremely effective. A cone biopsy involves a larger excision of cervical tissue and is generally reserved for adenocarcinoma in situ (the glandular ‘equivalent’ of CIN3), disease going up the cervical canal that cannot be fully visualised at colposcopy, or if invasive disease is suspected.

Patients treated for adenocarcinoma in situ, despite clear margins on cone biopsy, are at ongoing risk for developing further pre-invasive or invasive disease long term, and are therefore advised to have a completion hysterectomy (with ovarian conservation) once childbearing is completed.

16

Risk factors for cervical cancer

smoking,
early coitus,
multiple partners,
multiple pregnancies,
poor general health,
poor nutrition
a genetic predisposition to cervical cancer.
?COC makes HPV more virulent

Lifestyle factors include:
prolonged stress,
eating disorders,
poor diet,
excessive exercise and inadequate rest.

Illnesses that increase a woman’s risk include diabetes and immune disorders. Immunosuppressent agents also increase a woman’s risk.

17

Presenting symptoms

Abnormal bleeding e.g. persistant post coital bleeding

Advanced disease: Pain (particularly sciatic type pain), pressure symptoms and sometimes vaginal passage of urine or faeces

18

Radical hysterectomy

compared to a simple hysterectomy to achieve adequate clearance from the tumour, a vaginal and paracervical cuff of tissue is excised in continuity with the cervix. Much of the morbidity of this procedure comes from the additional dissection required to attain lateral clearance (bladder and bowel dysfunction) but this is usually temporary.

19

Radical trachelectomy

in patients with no lymph vascular invasion (LVSI) and tumours <2cm who want ongoing fertility, this procedure involves radical excision of the cervix with a vaginal and paracervical cuff, with reanastamosis of the vagina to the isthmus of the uterus with or without cerclage. This procedure enables the patient to undergo future childbearing, can be performed vaginally, laparoscopically or abdominally, and is combined with a pelvic lymphadenectomy.

20

Chemoradiation

definitive radiation with concomitant chemotherapy (weekly cisplatin 40mg/m2). Chemoradiation compared to radiation alone for the treatment of cervical cancer has been shown to provide a 30–50 per cent reduction in the risk of death, and is now the preferred option for the treatment of cervical cancer

21

HPV vaccine

- humoral antibodies that neutralise HPV before it can affect cells.
- Prevent establishment of persistent infection
- Gardasil protects against 6, 11, 16 and 18 (90-100% protection)
o Genital warts
o CIN
- (Cervarix is only 16 and 18)
- 3x intramuscular doses during 6 months.
- Prior to intercourse
- Routine is to immunise 11-12yr olds.

Vaccine free to girls born after January 1st 1990 or 1991, starting Dec 2011
Now year 8 offered vaccine
Can vaccinate sexually active girls
Can vaccinate girls with known HPV infection
Can vaccinate girls with previous warts or CIN
Need for ongoing smears should be recommended
Pregnancy category B2 however recommended to differ until after pregnancy (even if mid regime)
Can offer to women over 26yrs however is not endorsed as peak HPV infection is 5yrs after intercourse
Is approved for males 9-15yrs

22

3 types of cancers of the cervix?

Squamous cell carcinoma (70-80%)
- keratising
- non keratising
- small cell squamous

Adenocarcinoma (10-15%)
- mucinous
- adenoasquamous
- clear cell

Epithelial- eg neuroendocrine, undifferentiated..

23

How does squamous cell carcinoma develop?

Squamous cell carcinoma
- arises at squamocolomnar junction
- after infection with HPV (oncogenic serotype 16 and 18)
- most women clear the virus
- preinvasive dysplasia develops
- molecular alterations complex and not well understood
- cancer arises from an interaction of
o environment
o host immunity
o genomic variations

The oncogenic serotypes are able to integrate into human genome.
- amplification
- replication
- E7 oncoprotein binds to tumour suppressor gene- retinoblastoma, E6 oncoprotein binds to p53.
- This leads to unregulated cell
- They are then “immortalised” or hard to kill

24

How can cervical cancer spread?

can either grow into canal, or out to visible cervix

growth tracks through uterine arteries for haematogenous spread
drain into parametrial and paracervical lymph nodes
also drainage through cardinal ligament into a ureteric node
(need to be removed during parametrial resection in hysterectomy)

From there to pelvic nodes
- obturator
- common iliac nodes

Note: posterior cervix can drain through rectal lymph nodes
(remove with uterosacral ligaments during hysterectomy)

25

Bad prognostic signs for cervical ca

- Advanced FIGO stage
- Depth of tumour
- Tumour dimensions
- Vaginal or parametrial involvement
- lymphovascular space invasion
- nodal metastases (ie one vs multiple) (microscopic vs macroscopic)
- extension to pelvic side wall, ureteral blockage
- bladder invasion

26

Adenocarcinoma

(15%)
- may be more advanced before becoming clinically evident
- mucinous endocervical adenocarcinomas are the most common
- (can get neuroendocrine tumours of cervix too)

Gynaecology Oncology Group have shown Stage 1B squamous and adenocarcinoma are similar.
FIGO has also shown no difference in the survival of stage 1

However for more advanced stage disease adenocarcinoma looks to be worse

27

Follow up after treatment

Follow up
- MRI at 3 months
- Offer HRT to all premenopausal, prior to treatment
- Smears are performed but difficult to interpret
- Clinical exam
- 3 monthly for two years, 6 monthly to complete 5 years

28

Complications of surgery

- ureteral stricture
- bladder dysfunction
- constipation
- wound breakdown
- lymphocyst
- lymphoedema
- (radiotherapy after will increase risk of these complications)

29

Radiotherapy complications

- altered sexual function (shortened vagina)
- dysparaeunia
- psychological factors
- vaginal stenosis
- bowel and urinary fistulas
- enteritis/ proctitis
- bowel obstruction