Cervix

Introduction

The following links provide general information about cervical cancer.
http://emedicine.medscape.com/article/402329-overview
http://en.wikipedia.org/wiki/Cervical_cancer
http://www.tatamemorialcentre.com/cancerinfo/cervical/cervical.htm

Images of Cervical Cancer-
http://www.gfmer.ch/selected_images_v2/detail_list.php?offset=0&cat1=4&cat3=133&stype=d
http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=4&cat3=135&stype=d

Video on Histopathology
http://www.youtube.com/watch?v=zB47nE-i8dQ

Risk Factors

1) Human papilloma virus infection (HPV)
All cervical carcinomas are considered to have HPV infection as a co-factor. The high risk HPV's 16, 18, 31
and 45 are considered as sexually acquired and even though they are required, they alone are not sufficient to
cause cervical cancer. Genetics, other infections like chlamydia are also considered important in aiding HPV.
Positive smoking history and low socioeconomic condition are also risk factors.

Questions to Ponder
1.How to identify chronic HPV infected people who are at higher risk to develop malignancy?
2.Indian Association of Pediatrics recommends Cervical Vaccine, do we recommend it?
2) Smoking — Causes the body to be exposed to many cancer causing agents which are transported by blood stream to various organs to cause the damage.
3) Immunosuppression — Predisposes to infections including HPV
4) Multiple full term pregnancies — No body really knows why this happens. Probably for multiple pregnancies the lady has to have multiple unprotected sexual exposures that predisposes her to HPV infection.
5) Poverty — Poor women do not have access to health care and screening; which means they may not get screened or treated for pre-cancerous lesions.
6) Diet — Obesity or over weight women tend to develop more adenocarcinomas than there counter parts. Eating fruits, vegetables makes sense.
7) Family History
8) Diethylstilbesterol (DES) — Ladies whose mothers took DES (when pregnant with them) develop clear-cell adenocarcinoma of the vagina or cervix more often than would normally be expected. The rate is 1 in 1000 women who took DES during pregnancy, which is very low to be scared off.
9) Young age at first pregnancy — Age < 17 years when they had their first full-term pregnancy are almost 2 times more likely to get cervical cancer later in life in comparison to women who waited to get pregnant until they were 25 years or older.
10) Oral contraceptive pills — There is evidence that taking oral contraceptives (OCs) for a long time increases the risk of cancer of the cervix. The risk of cervical cancer was doubled in women who took birth control pills longer than 5 years, but the risk returned to normal 10 years after they were stopped.
11) Chlamydia infection — Very common pathogen for genital tract infections or pelvic inflammatory diseases in women and a mjor cause of infertility, many times the women may be asymptomatic.

Pathology

Squamous cell carcinoma — Commonest cervical cancer
Adenocarcinoma — Common in young cervical cancer patients.
Adenosquamous —
Small cell carcinoma — Worst Prognosis

Staging

Stage 0 carcinoma-in-situ
Stage I the tumor is confined to the cervix

IA microinvasive disease, with the lesion not grossly visible: no deeper than 5 mm and no wider than 7 mm

IA1 invasion <3 mm and no wider than 7 mm
IA2 invasion >3 mm but <5 mm and no wider than 7 mm

IB larger tumor than in IA or grossly visible, confined to cervix
IB1 clinical lesion no greater than 4 cm
IB2 clinical lesion greater than 4 cm

Stage II extends beyond the cervix, but does not involve the pelvic side wall or lowest third of the vagina

IIA involvement of the upper 2/3 of vagina, without lateral extension into the parametrium
IIB lateral extension into parametrial tissue

Stage III involves the lowest third of the vagina or pelvic side wall, or causes hydronephrosis

IIIA involvement of the lowest third of the vagina
IIIB involvement of pelvic side wall or hydronephrosis

Stage IV extensive local infiltration or has spread to a distant site

IVA involvement of bladder or rectal mucosa
IVB distant metastases

+ PREVENTION
HPV vaccination against 16 and 18 is being claimed to prevent carcinoma cervix. All the trials done have not had, and cannot have carcinoma cervix as end point. Rates of CIN 3 as end point has been argued as a good surrogate indicator for reduction in carcinoma cervix incidence. The vaccine is being recommended in age group of 9 to 26 years. The immunity proven is for 5 years. There is no clarity about booster dose. Cross infection from other HPV is debatable. Risk of other STD's and other causal factors need to be elucidated. Screening is a must and people immunised cannot be exempted from screening.

Screening

Cervical cytology screening should be initiated within three years of vaginal sexual activity. Screening should be done until 3 annual consecutive PAP smears are negative. Screening should continue every 2-3 years after three negative annual PAP tests. One can stop screening if age>70 with previous 10 years history of negative PAP test.

Management

FIGO Stage IB1 and IB2 —
i) Surgery - Preferred in young patients with aggressive histologies (adenoca, small cell, neuro endocrine).
ii) Radical Radiation Alone — 4500-5000 cGy @ 1.8 - 2 Gy per fraction over 5-6 weeks, interspersed with Intracavitory brachytherapy HDR 6-9 Gy per fraction x 3/4 insertions one week apart. Total dose 8000 cGy to point A. Overall treatment time <8 weeks.

FIGO Stage IIA/ IIB —
i) Radical Chemoradiotherapy — 4500-5000 cGy @ 1.8 - 2 Gy per fraction over 5-6 weeks, interspersed with Intracavitory brachytherapy HDR 6-9 Gy per fraction x 3/4 insertions one week apart and concomitant weekly cisplatinum chemotherapy (30-40 mgs/m2). Total dose 8000 -8500 cGy to point A. Overall treatment time <8 weeks.
ii) Neo-adjuvant chemo to downstage followed by operation in trial settings only.

FIGO Stage IIIA/B —
i) Radical Chemoradiotherapy — 4500-5000 cGy @ 1.8 - 2 Gy per fraction over 5-6 weeks, interspersed with Intracavitory brachytherapy HDR 6-9 Gy per fraction x 3/4 insertions one week apart and concomitant weekly cisplatinum chemotherapy (30-40 mgs/m2). Total dose 8500 cGy to point A. Overall treatment time <8 weeks. Some institution practice response assessment and parametrial boost of 500 cgy at the end. Note: One can also do interstitial brachytherapy instead of Intracavitory brachytherapy for selected patients.
iii) Selected patients may go on to receive Para-aortic radiation.
ii) Neo-adjuvant and or adjuvant chemotherapy to downstage followed by radical chemort in trial settings only.

FIGO Stage IVA —
i) Radical chemoradiation in highly selected patients who have minimal bladder involvement only. Need discuss the complication in details with high risk consent. These patients need careful monitoring during treatment as they are prone to develop fistula's.
ii) Palliative radiotherapy or chemotherapy. Treatment to be tailored as per patients needs and response.

FIGO Stage IVB —
i) Palliative treatment.

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