Huma Azam Khan TMO,GAW KTH
cancer is the second most common malignancy in women worldwide, and it remains a leading cause of cancer-related death for women in developing countries
WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre) 2010
49.25 million women at risk for cervical cancer (Female population aged >=15 yrs)
Annual number of cervical cancer cases 11688
Annual number of cervical cancer deaths 7311
papillomaviruses is the essential
there is a clear association between cervical cancer and sexual activity. multiple sexual partners. promiscuous male partners. and history of sexually transmitted diseases
. Major risk factors are sex at a young age. Human
prerequisite for the development of cervical malignancy.
simplex virus 2 and chlamydia trachomatis increases the risk of progression to advanced
preinvasive or invasive cancers
Progression to CIN lesions and ca cx seems to be increased among HIV carries and AIDs patients
and stress-related disorders
contraceptives Multiple pregnancies Low socioeconomic status Race-incidence higher in blacks/Hispanics Diethylstilbestrol (DES) Family history
Source: American Cancer Society
More than 170 subtypes of HPV have been identified
HPV is the essential prerequisite for the development of cervical malignancy.
Prevalence of HPV in CA cervix is 99.
On the basis of oncogenic potential
Extrachromosomal HPV DNA
Integrated HPV genes
Deregulated expression of HPV E6 and E7 Interactions with cellular regulatory proteins
Benign growth or wart Malignant tumour
HPV is Epitheliotropic
No viremia Infection is confined to where it initiated Spreads by infected cell dividing Sexual contact ONLY
• CIN1 or mild dysplasia
Low 60% Grade will regress CIN spontaneously OR Aprox Low grade 10% will Squamous progress intraepithelial to higher grade neoplasia lesions
• CIN2 or moderate dysplasia
High gradeCIN OR CIN3 will Aprox 36% High grade Squamous develop invasive Ca if intraepithelial left untreated neoplasia
• CIN 3
• Carcinoma In Situ
Risk factors for progression of low-grade SILs
type of viral infection duration of viral infection. Diabetes HIV
predicting a higher risk for progression)
environmental factors such as
multiparity or poor nutritional status. (with high-risk HPV type and persistent infection host conditions that compromise immunity.
. vitamin deficiencies. oral contraceptive use.
large cell or small cell
(10% of all cases)
adenocarcinoma and squamous cell carcinoma). Squamous
cell carcinoma –90% keratinizing or non-keratinizing.
Rare types Endometriod adenocarcinoma Small cell carcinoma. Lymphoma (many cell types) Mesonephric carcinoma Undifferentiated Carcinoma
. Sarcoma (cell types vary).
weight loss fatigue.
inter-menstrual bleeding (IMB) post-coital bleeding (PCB) post-menopausal bleeding (PMB) vaginal discharge (blood stained) pelvic pain Dysparunia loss of appetite.
pain leg pain swollen legs heavy bleeding from the vagina bone fractures leakage of urine or faeces from the vagina (rarely)
Bimanual examination findings often reveal pelvic and/or HepatomegalyIf the disease involves the liver. tumor
Leg edema suggests lymphatic/vascular obstruction from
In early-stage cervical cancer.
parametrial metastasis. or mass.
Rectal examination may reveal an external mass or gross
blood from tumor erosion. Pulmonary metastasis presents as pleural effusion or
bronchial obstruction. ulcer. findings can be relatively normal. with gross
The cervix may be abnormal in appearance.
carcinoma Pelvic inflammatory Disease Vaginitis
When to start screening
Age 21 regardless of the age of onset of sexual activity Should be avoided before age 21
Source: American congress of obstetricians and gynecologists (ACOG)
Every 2 years from age 21-29 years Every 3 years for women above age 30 years with a history of 3 negative cytology tests Annual screen (or more) if high-risk: HIV+. history of
DES. prior CIN2/3 or cervical cancer
When to stop screening
Between age 65-70 yrs with 3 consecutive normal cytology tests and no abnormal tests in the past 10yrs
screening may be discontinued Women for whom a negative history cannot be documented should continue to be screened.Screening Post Total Hysterectomy
If removal for benign disease and no history of high-grade CIN or worse.
Screening among those immunized against HPV 16/18
Recommendations remain the same regardless of vaccination status
Pap smear Liquid Based Cytology HPV genotyping
Greater sensitivity than liquid cytology
It has poorer specificity compared with cytology reduced the incidence of cervical cancer by 60-90%
• The false-negative rate of a Pap test is 20%. which mostly results from sampling error • Physicians can reduce sampling error by ensuring adequate material is taken from both the endocervical canal and the ectocervix
A gynecologic sample is collected using a broomtype or cytobrush/spatula cervical sampling device
. the sampling device is rinsed into a ThinPrep vial containing PreservCyt® transport medium
The sample vial is capped. and sent to the laboratory for slide preparation. labeled.Instead of smearing the cells on a slide.
then additional workup with a colposcopy is indicated. if a woman has a pap test result showing atypical squamous cells of undetermined significance (ASCUS) and a positive HPV test.HPV DNA tests
• HPV testing is highly sensitive and moderately specific for cervical intraepithelial neoplasia (CIN) grade 3 or worse • The HPV test is also useful for interpreting equivocal results from a Papanicolaou test.
Abnormal Cervical Cytology
To exclude an invasive process
Acetic acid colposcopy
Acetic acid (dilute vinegar) is applied to the cervix. Abnormal areas such as CIN will tend to turn white (acetowhite)
Schiller’s iodine test
pre-cancerous abnormalities may not stain with iodine
Taking a biopsy
Loop TZ excision(LLETZ/LEEP) Laser TZ excision Knife cone biopsy Hysterectomy
Cryosurgery Electrodiathermy Cold coagulation Carbon dioxide laser
6—12mon Annual smears for 9yrs 3 to 5 yearly smears
6—12—24 mon then 3 to 5 yearly screening cytology
Once ca cervix is confirmed,the following information should be obtained Tumour histological type Differentiation Size Pattern of invasion Lymphovascular space invasion
Complete Blood Cell Count Serum Chemistry
RFTs LFTs possible metastatic disease
CXR…pulmonary metastasis Ct scan of abdomen and pelvis MRI or PET-CT scanning is now recommended for patients with stage IB2 disease or higher
Cystoscopy sigmoidoscopy Barium enema
should not be routinely performed for staging purposes. Only if imaging cannot exclude bladder or bowel involvement.
Paracervical Obturator Internal
iliac External Iliac Common Iliac
in collaboration with the World Health Organization (WHO). and
TNM system of the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC)
.FIGO and TNM Staging
Two staging systems are frequently used in cervical cancer:
Tumor is confined to the cervix
Only identified microscopically
<4cm Stage 2A2……>4cm
Beyond the uterus but not pelvic sidewalls or lower third of vagina
Pelvic side walls and/or Lower third of vagina
Invades lower third of vagina but not pelvic sidewalls
Extends to pelvic sidewalls and/or hydronephrosis
Extends beyond true pelvis or invades rectal or bladder mucosa
Invasion of bladder or rectal mucosa
Spread outside True pelvis
chemotherapy or radiation provides symptom palliation.
Stage Age Health status In general surgery is an option in early disease Radiation can b used in all stages Chemotherapy used in advanced disease In patients with disseminated disease.
. percutaneous endoscopic gastrostomy tubes or hyperalimentation
.appetite stimulants can be prescribed If pt can not tolerate oral intake or have extensive bowel obstruction .Nutrition
Proper nutrition is important Nutritional supplements should be used in patients with weight loss In case of severe anorexia.
hysterectomy Radical hysterectomy Radical radiotherapy Chemotherapy Pelvic Exenteration
is a procedure in which a "cone" of tissue is removed Knife.LLETZ)
. Laser. or Electrocautery(LEEP.
incompetent cervix.cervical stenosis.Knife cone biopsy/excision
Risks:provides requiresthe GA.(no scarring that as would be in
. and in rare cases Benefits: cleanest specimen margins for further histologic hemorrhaging requires anLEEP) emergency hysterectomy study .
more effective then laser cervix cervical stenosis and incompetent
.local Risk of infection anesthetic.LEEP/LLETZ excision
Disadvantage:Small risk of bleeding Advantage :office procedure.
quick damage procedure no or very little chance of bleeding
.CO2 Laser excision Disadvantage :Specimen can not be out evaluated accurately because of thermal Advantage:Can be performed as an outpatient procedure.
Surgical removal of uterine cervix Fertility preserving procedure
Women wanting conception Tumor size <2cm Stage 1A1-1B1 No evidence of pelvic LN metastais Tumor atleast 1cm away from internal os on MRI
cervix.Removal of uterus. upper third of vagina and parametrial tissue with or without pelvic lymphadenectomy
Primary treatment Adjuvant after surgery Palliative therapy
Types External beam radiotherapy or Teletherapy(50Gy)
Brachytherapy(short wave radiotherapy delivered by the insertion of applicators into the uterus via the vagina)(70-80Gy)
diarrhea. rectal discomfort.. or bleeding Dysuria Frequency Nocturia
Late sequelae.1-4yrs after treatment
Rectal/vaginal stenosis Small bowel obstruction Malabsorption Chronic cystitis
Toxicity is increased
. although 5-fluorouracil also is used frequently
Incase of metastatic disease apart
from cisplatin Topotecan. ifosfamide. Cisplatin is the agent used most
. including the uterus. vagina. Less than 50% of patients survive five years after TPE. and rectum Total pelvic exenteration (TPE) is a high morbidity procedure. cervix. bladder.
the procedure involves en bloc resection of all pelvic structures.
treated with local ablative or extricative measures such as cryosurgery. After local treatment. laser ablation. and loop excision.
. Hysterectomy should be reserved for patients with other gynecologic indications to justify the procedure. these patients require lifelong surveillance.
Lymph node dissection is not required
.The treatment of choice is surgery Conization with free margins Total hysterectomy
Patients with medical comorbidities who are not surgical candidates can be successfully treated with radiation.
standard treatment consists of complementary concomitant chemoradiation.
Options consist of conization or Trachelectomy in young patients and simple or radical hysterectomy Pelvic lymphadenectomy is required.(5% chance of nodal involvement) In patients with pelvic node involvement.
pelvic lymphadenectomy(fertility preservation.
radical trachelectomy.small tumour.no LN involvement) radical hysterectomy plus bilateral pelvic lymph nodes dissection Radical radiotherapy
surgical expertise is not available in women with large tumours (> 4 cm in diameter) or in women who are not medically fit for surgery
In cases where positive LNs are encountered the management is controversial
Abandonment of surgery in favour of chemoradiation
Radical surgery completed f/b adjuvant radical radiotherapy
Treatment of choice Radical radiotherapy or Chemoradiation
Palliative surgical procedures are used
Defunctioning colostomy Percutaneous nephrostomy
Symptom status at the time of recurrence is a significant predictor of survival.
Median survival rate in Sypmtomatic recurrence…11month Asymptomatic recurrence…42months
Site and extent of recurrence Primary therapy Time elapsed since primary treatment The patients wishes Patients general health
Single agent chemotherapy pelvic radiation Prior surgery Combination chemotherpy distant
Radical hysterectomy Prior radiotherapy
If recurrence is <2cm
PET-Ct to exclude extra pelvic disease
Pelvic exenteration C/I leg pain Leg edema hydronephrosis
Pain Renal failure(bilateral ureteric obstruction due to disese process or raditherapy) Thrombosis Hemorrhage Malodorous discharge Lymphedema Fistule-rare but grave feature
Direct nerve infiltration or nodal enlargment impinging on pelvic nerves Option Oral analgesics Opiates Fentanyl patches Nerve blocks gabapentin
Bilateral ureteric obstruction(bilateral parametrial infiltration or extrinsic compression or radiation
Lack of consenses on optimal managment
Options Percutaneous nephrostomy Retrograde stenting Urinary diversion
LMW Heparin recommended
Result of erosion of blood vessels on the surface of an exophytic or ulcerating growth
Options Oral tranexamic acid Withholding NSAIDS Vaginal packing A single fraction of radiotherapy
diversion Ileostomy or colostomy
No adverse effect on prognosis or natural history of ca cervix
Immediate treatment irrespective of stage
LLETZ/Cold knife conization 6wks postnatally
Elective C/S Early stage 1A1-1B1
Treatment delayed till fetal maturity
Advanced cancer (1b2 or greater Delay upto 4wks can be considered Classical C/S
Aimed to detect recurrent disease Assess treatment related morbidity Analyse psychosocial/sexual morbidity
Every 4mon for 2yrs MRI/Ct should be done whenever recurrence is suspected PET-Ct more sensitive
the 5-year survival rates are as follows:
Stage I .Less than 30%
.Greater than 90% Stage II .Prognosis of cervical cancer depends on disease stage.60-80% Stage III .Approximately 50% Stage IV . In general.
barrier protection and/or spermicidal gels during sexual intercourse are protective HPV vaccines Cervarix®, (GSK Biologicals) Gardasil® (Merck) Three 0.5ml injections are given at 0,2 and 6month
Immunity has been demonstrated for 5 yrs Longterm followup studies are ongoing.