CARCINOMA CERVIX

INCIDENCE 4-15 in developed countries 30-40/lac in developing countries Accounts for 60% of malignancies in developed &80% in developed countries . Life time risk 1.9( USA), 2.2(india)

Magnitude of the problem

Incidence is decreasing in developed countries Pap smear has reduced incidence by 80%& death by 70% Preventable disease- availability screening, diagnostic, therapeutic procedures. 1 million fresh cases/year across the globe Most common CA in developing countries

ICMR REPORT

II nd commonest cancer in women Relative proportion varies 14-24 Causes- economic factor, sexual behavior & degree of effective mass screening

Risk factors

Early intercourse(<16yrs) Early age of pregnancy Too many/ too frequent pregnancy LES Multiple sexual partners STDs HPV 16,18,33,35 HIV Death of wife due to ca cx OCPills smoking

Pathogenesis

Cx epithelium-> infection->hpv dna integration to human genome-> up regulation of viral oncogenes-> expression of E6&E7 oncoproteins ->interference with tumor suppressor genes-> host cell immortalization, HPV induced euplastic transformation

HPV TRIAGE

Pap smear test -> atypical -> Hpv testing- high risk positive Colposcopy This strategy highly effective in diagnosing CIN II & III lesions reduces load on colposcopy clinic

Gross pathology

Ecto-cervix- 80%, endocx- 20% Naked eye exopytic- from ectocx & forms friable masses filling upper vagina Ulcerative- lesion excavates the cx often involves vaginal fornices Infiltrative- found in endocervical growth-> expansion of cx -> barrel shaped cx

HISTOPATHOLOGY

Squamous cell carcinoma is the commonest (8090%) Well differentiated, moderately differentiated, poorly differentiated Source- SCJ, healing erosion, squamous metaplasia of columnar epithelium, squamous cell rests in ectocx SCC-> i) large cell keratinising ii) large cell non keratinising iii) small cell type

HISTOPATHOLOGY

Adenocarcinoma (10-15%) develops from endocervical canal- from lining epithelium/glands Occurs at young age 80% purely endocervical type Others- endometroid, clear, adenosquamous, or mixed Adenoma malignum- well differentiated adenocarcinoma with favourable prognosis

Mode of spread

Direct adjacent structures-, uterus, vagina, parametrium, paracervical, paravaginal tissues. Through-> rectum, pubocervical-> bladder Lymphatics- parametrial,obturator,internal iliac external iliac, sacral nodes Secondary nodes- common iliac, inguinal, para-aortic nodes Sentinal node 85% drainage to single node detected by methylene blue injection in to tumour, lymphoscintigraphy Blood spread- veins- lungs,liver,bones Direct implantion

Involvement of lymphnodes in different stages

stage 0 Ia1 Ia2 Pelvic nodes% 0 0-0.5 5 Paraaortic % 0 0 <1

Ib
II III IV

16
30 44 55

2
15 30 40

STAGING
For determining prognosis To formulate line of treatment To compare results FALLACIES -difficult to assess lymph node involvement on clinical examination adversely affects prognosis - Difficulty in assessing parametrium(inflammatory/malignant induration)

BASIS

CLINICAL EXAMINATION Pelvic examination- p/s,p/v,p/r- under anesthesia Supplemented by Cxr, IVP, cystoscopy, proctoscopy In case of infection antibiotic to be given prior to staging Final stage cannot be changed once therapy has begun Choose lower stage if in doubt CT,MRI,PET, lymphangiography- detect LN,& parametrium .MRI- tumour volume, parametrial extension.but these donot change FIGO stage

FIGO staging of carcinoma cervix

Preinvasive carcinoma Stage-0 carcinoma in situ Invasive carcinoma Stage-I strictly confined to cx Stage-Ia- preclinical diagnosed only on microscopy Stage-Ia1 minimally microscpically invasive <3mm Stage-Ia2 invasion>3mm<5mm, width<7mm, Stage-Ib greater than Ia2 Stage-Ib1 <4cm in size Stage-Ib2 >4cm in size

FIGO STAGING

Stage-II extends beyond cervix but not to pelvic wall, involves vagina but not lower 1/3rd Stage-IIa no obvious parametrial involve ment Stage-IIb obvious parametrial involvement

FIGO STAGING

Stage-III carcinoma extends to pelvic wall, involves lower 1/3rd of vagina, hydronephrosis/nonfunct kidney Stage-IIIa no extension to pelvic wall but to lower 1/3rd Stage-IIIb extension to pelvic wall&/ hydronephrosis/nonfunct kidney

FIGO STAGING

Stage IV extension beyond true pelvis, or clinically has involved mucosa of bladder/rectum Stage IVa spread to adjacent organs Stage IVb distant metastasis

prognosis

Stage Site- endocervical dangerous Depth<1 cm, <LN -> ^ survival Differentiation Age Paraaortic node involvement< survival by 50% Hpv

Diagnosis

early ca limited to cx Survival I=80-100%,II=55-70% Preclinical- biopsy/cytologycolposcopy/schillers guided biopsydiagnostic conisation- depending on depth of stroma staging done Stage 0, stage Ia, stage Ib

Diagnosis
Stage 0 BM intact stage Ia BM disrupted Mean age 38-42 Majority asymptomatic- diagnosis by conisation Stage Ib symptoms- menstrual abnormalities, white discharge

diagnosis

p/s-> erosion/ nodular growth, ulcer Bleeds to touch. p/v-> indurated, friable, bleeding to touch p/r-> parametrium free Confirmation by biopsy

Advanced carcinoma

Symptoms: irregular/continuos bleeding Offensive discharge Pelvic pain Leg edema Bladder symptoms Rectal symptoms Ureteral obstruction

Advanced carcinoma

p/s-> ulcerative / fungating growth p/v -> induration / extent of growth p/r-> parametrium/ extention to lateral wall/rectal involvement Smooth induration- infetion, nodular- malignancy Confimation of diagnosis- biopsy

Differential diagnosis

Cervical tuberculosis Syphilitic ulcer Cx ectopy Incomplete abortion Fibroid polyp

complications

Haemorrhage Ureteric colic-> pyelitis, pyelonephritis, hydronephrosis Pyometra VVF RVF

Causes of death

Uremia Hemorrhage Sepsis Cachesia Metastases-> lung-36%, LN-> 30%, bone>16% , abdominal cavity-> 7%

management

Prevention-> high risk male/female Use of condom Hysterectomy-(stump ca 1%) Recombinant vaccination Secondary prevention by screening Down staging screening(WHO 1986)-> diagnosis by p/s Normal cx-> pink,smooth, round, does not bleed to touch Abnormal cx-> reddish,red/white area of patch, bleeds to touch

curative

Treat ment decision should be made by gynaecologist and radiotherapist Improve general health , anemia, malnutrition Modalities Primary surgery Primary radio therapy Chemotherapy Combination therapy

surgery

Radical hysterectomy abdominal->Wertheim vienna 1898, okabayashi 1921, meigs usa-1944 Vaginal-> schauta of vienna-1902, mithra india- 1957 Structures removed- uterus, tubes, ovaries,upper half of vagina, parametrium, primary lymphnodes Limited to early stages

Advantage of surgery over RT

Better staging stage+LN=> better survival Ovarian function preserved Transpositioning of ovaries possible Normal Vagina maintained Psychological benefit

Special indications

PID-acute/chronic Pelvic kidney Fibroid,prolapse,ovarian tumour,vvf Young patient Vaginal stenosis Recurrance after RT adenoCA, adenosquamousCA

Post op complications

Major- per op- hemorrhage,injury,anaesthetic Post op- shock,urinary, pyrexia, Vvf,uvf,bladder dysfunction,pyelonephritis,rectal dysfunction Lymphocyst, dyspareunia& recurrance Mortality<1%

Pelvic exenteration
Ultraradical surgery- brunschwig Stage IVa Central pelvic recurrent CA Resectable tumour mass Absence of ureteral obstruction,sciatic pain,unilateral edema Woman ready to accept stomas Contra indications- distant metastasis

TYPES

Anterior Posterior Complete/total Laparoscopic radical hysterectomy

Primary radiotherapy

First malignancy to be treated- by margaret cleves 1903 Chemoradiation IIb- Iva External photon beam radiation, brachytherapy Advantages- wider applicability,survival85%,less primary mortality/morbidity,individualisation possible

Early stages

Brachy therapy radium 226Ra, cesium 137 Cs or cobalt 60Co Tandems-uterine cavity, ovoids& colpostats-vaginal vault under GA Methods- paris, manchester- strength small exposure time more Stockholm- large high intensity- less exposure time Remote after loading fletcher suit

Draw backs of RT

Strictures Fistulas Vaginal fibrosis, stenosis rad- menopause, fibrosis of bowel / bladder Ovarian trans position

Calculation of dose

Point A 2cm above & lateral to ext os Point B 2cm above 5cm lat to same plane Point A- 7000-8000 cGy Point B-2000 cGy EBRT- 4000 cGy IMRT Advanced cases- hyper baric oxygenation recurrent CA- EBRT Ca after TAH- EBRT 4500cGy Stump CA- tandem+ EBRT

Combination therapy

Surgery followed by RT Positive LN Accidental diag of CA after TAH Positive tissue resection margin + RT followed by surgery Endocervical Ca barrel CX Bulky tumour Neoadjuant chemotherapy LARVH,radical vaginal trachelectomy

Planning of treatment

Early- Ia- Ia1- TAH,conisation, Ia1(3mm inv)extrafascial hysterectomy(type 1), Ia2- radical hysterectomy Ia1/Ia2- lymphovascular invasion- type II radical Ib,IIa- typeIII, EBRT if nodes+ / primaryRT with platinum chemo therapy Radical trachelectomy

Relatively advanced disease

Stage IIb- RT+ cisplatin Advanced disease IIa-IVa= primary chemoradiation+cisplatin based chemotherapy disseminated: IV a- chemo/palliative radiation

Palliative therapy

Symptomatic therapy Foul smelling discharge- antimicrobial cream Bleeding- palliative radiation(180200cGy/day), packing with monsels solution Pain- NSAIDS, p.radiation- 3000cGy Diazepam/amitryptyaline Neuropathic pain - blocks

pregnancy

Diagnosis cone biopsy Micro invasive- follow up Advanced- Ist tri same as non pregnant Late- classical cs followed by radical surgery/RT Stage the imp for prognosis

Results
stage IIa IIb IIIa 5yr survival 76.0 73.3 50.5

IIIb
IV a IVb

46.4
29.6 22.0

Recurrent cervical cancer

M.c. site- pelvic side wall Follow up majority of recurrancies- 2 yrs Interval 3-4 months stump carcinoma 1% Radical parametrectomy/ EBRT