Cervical cancer is the most common malignancy in females. About 3,70,000 cases diagnosed annually; 78% of the cases in developing countries. It ranks the first carcinoma and breast carcinoma ranks second. Ratio between cervix and breast cancer is 3:1. But in developed countries the ratio between and cervical CA and breast CA is 1:3 where cervical CA ranks the second. lnvasive cancer of the cervix is considered a preventable disease because it has a long preinvasive state, cervical cytology screening program and effective treatment of preinvasive lesion As a result cervical cancer is being diagnosed earlier which leads to better survival rate. This is why the world-wide incidence of cervical cancer is decreasing. Commonest cancer among women.
• Burden of Ca cervix in India
• New cases = 130,000/year
• Deaths = 70,000/yearProjected at 100,000 deaths by 2010
• > 200 females die each day
• One women is dying every seven minutes
• Eight women die each hour
• It has a bimodal distribution with peak: 35-39 years, 60-64 years
• In India the prevalence is higher amongst the comparatively younger age group.
• Major factors influences the prevalence of CA cervix in a population are economic factor, sexual behavior and degree of effective mass screening
• Risk factors for Ca Cervix
• Sexual activity at a young age
• High number of pregnancies
• Cigarette smoking
• Long-term use of oral contraceptives
• Other sexually transmitted infections (e.g., HIV and chiamydia
• malnutrition,
• Unhygienic genital health
• lndiviJual's immune status
1. Early age at first sexual intercourse (<1 óyears) has already been discussed that at menarche the SCJ is at active metaplastic state which is more vulnerable to oncogenic agents like sperms, seminal fluids, histones, infections with Trichomonas, chlamydia, HSV-11, H PV- 1 6,18.
2. Early age at first pregnancy.
3. Multiple sexual partners.
4. High parity.
5. Sexually transmitted diseases - syphilis prevails 3.5 times more commonly in CA cervix.
Chlamydia trichomatis and CMV are strongly associated with cervical CA. Trichomonasis and candidiasis are found in CIN but not in invasive cancer.
6. Smoking It increases incidence by 2 folds.
Diminishes the immune function secondary to systemic effect of cigarette smoke and its biproducts or locally effect of tobacco specific carcinogens
7. Low socio-economic status Incidence is higher due to poor diet, low hygiene and risk of STDs.
8. IMMUNOSUPPRESSION
- Women who are infected with HIV infection have an elevated prevalence of human papilloma virus infection and persistence of HPV and cervical dysplasia.
- Incidence also occurs more in organ transplant patients.
9. RACE
- Highest incidence seen in black women as compared to white (3 times more) & Low incidence in Muslims (due to circumcision).
- Less in Jewish. Diet
- Low intake of Vit.A, deficiency of Vit.0 and folic acid shown to increase the risk.
- Oral contraceptives - Otherwise controversial but females using OCPs are relatively more sexually active, OCPs also act as steroids -decreases the immunity
- suppresses the P53 gene - increases self-proliferation for cervical dysplasia and leads to adeno - carcinoma.
- Husband whose previous wife died because of CA cervix. Human Papilloma Virus (HPV) lnfection:
• HPV infection has a central causative role in the etiology of cervical neoplasia. HPV are members of a large family of virus Papova viridae.
• Papilloma virus have a tightly coiled, circular double standard DNA molecules about 8000 base pairs in length The complete virion consists of a DNA core and surrounding proteins.
• HPV infects all surface epithelium including skin and mucus membrane.
• Approx. 100 types of HPV identified. More than 30 of which can affect the lower genital tract of female and there are 14 high risk HPV subtypes.
These are further subdivided into three subtypes according to risk for oncogenecity
1. Low oncogenic risk - 6, 11, 42, 43, 44 - causes low grade CIN and flat condylomata.
2. Inter mediate oncogenic risk - 31, 33, 35, 51, 52 - causes low grade and high grade CIN.
3. High oncogenic risk- 16, 18, 45, 46-invasive CA
• Two of high risk subtypes 16 & 18 are found in up to 62% of cervical carcinomas. HPV 18 is the most specific and is associated with tumour with a more aggressive clinical behavior but HPV 16 is the most commonly found and causes large cell Keratinizing squamous cell CA.Virus enters the genital tract by sexual contact and affects any part of the female genital tract.
• Virus have incubation period 1-6 months.
• After that the first lesion appears and there is a rapid and active growth of the virus, as well as immune response occurs in the host.
• After about 9 months of this activity two outcomes are expected
a) Immune response good - sustain clinical remission. Immune response is poor - persistent and recurrence disease Clinical Presentation:
HPV infection may not cause any symptom hence diagnosis is difficult to make. But it is possible by
- Clinical study.
- Cytology.
- Colposcopy.
- Histopathology.
- Molecular biology.
• Clinical diagnosis is based upon the warts on external genitalia, usually due to low oncogenic virus.
Detection of HPV Infection
Cytology HPV- DNA can be detected by
- PCR
- Southern blotting
- In Situ Hybridisation
- Dot Blot Hybridisation
- Hybrid Capture Technique
Target Population for HPV Screening
• A sexually active woman above the age of 30 years. VACCINES AGAINST HPV
- Bivalent vaccine - Against 16 and 18 viruses but also give cross protection against others. It is called Cervarix Quadrivalent vaccine against 6, 11, 16 and 18. (Gardasil or Silgard) give protection against genital warts
- Prophylactic vaccine is given as I/M in three doses at 0, 1 and 6 months. It is recommended only for girls up to the age of 26 years. But can be given to males or females age 10-12 years. Preferably before starting sexual activity
Available vaccine 1. Quadrivalent (against 6, 11, 16, 18) Gardasil dose 1st dose, 2nd dose at 2 months, 3rd dose 6th month
1. Bivalent(against 16, 18) Ceryarix dose i' dose, 2nd dose at 1 month, 3rd dose at 6 months
• Cervical Cancer Prevention Primary Prevention HPV information and prevention
Screening Behavioral modification Sexual precautions Prophylactic vaccines
• Secondary Prevention
CIN Detection and treatment
SCREENING
Do a good per speculum examination in good light
VIA_ Apply 3-5 % acetic acid to note any areas becoming white after acetic acidnapplication.
VILI_Apply lugos iodine to check dark mahgony or light mahgony area Paps smear should be taken once acute massive vaginal discharge is clear. Do not take smear during menstrual phase.
• No P/V before Pap smear
• No lubricant on speculum
• 3600 sweep with Ayre's spatula - smeared on slide
Screening is to be started at 21 years if married not before 21 years even if married for 3years. Co-testing means HPV with pap's smears.
21 years to 29 years-------- do only pap's smear. HPV NOT TO BE DONE
30years to 65 years --- only pap's every 3 yearly, if co-testing is done then every. 5 years.
After 65 years -- Stop if previous 3 negative smears.
After total hysterectomy -- no need if done for benign disesase
In case of abnormal pops smear refer the patient for colposcopy and biopsy if required.
DIAGNOSTIC METHODS
1. Colposcopy - All changes of CIN are exaggerated.
- Abnormal vessels - Loop, branching, reticular cork screw or 1i' shaped pattern.
- Irregular surface contour
- colour tone is yellow-orange but in intact sq. epithelium if is pink and in endocervical
epithelium is red.
Adeno CA does not have specific colposcopic appearance; abnormal blood vessels maybe seen.
2. Endocervical cureftings to rule out adeno CA. -
Biopsy In presence of obvious lesion Punch biopsy
Wedge biopsy
Ring biopsy (Ring of tissue from SCJ)Cone biopsy for adeno CA when there is no obvious growth.
Colposcopic directed biopsy - lesion can be delineated before taking biopsy by painting the cervix with Schiller1s iodine (5% iodine in 100% Kl) - stains normal cell mahogany brown and leaves abnormal cells unstained.
Tumour markers - sq. cell CA antigen <2ng/ml is normal, when raised - CA cervix.
PROCEDURES FOR STAGING
• Physical examination - P/V and P/R.examination
• Procedures:
- If there is obvious growth then cervical biopsy.
- If no obvious growth - then colposcopic examination with cervical biopsy and endocervical curettings.
- If diagnosis cannot be established with colposcopy and directed biopsies then cervical conization to be done.
- Cystoscopy - If histopathology positive.
- Proctoscopy.
- Radiological Studies:
- Intravenous pylogram. Barium enema. Chest X-ray. Skeletal X-ray.
- Optional Studies: Not allowed by FIGO
- CT Scan / MRI, Ultrasonography, ,Lymphangiography, PET Scan
Stage | Descrition |
I | The Carsinom is Stricly confirmed to the cervix (extension to the uterin corpus should be disregarded) |
IA | Invasive cancer identified only microscopically. (All gross lesions even with superficial inveasion are Stage IB cancers.) Invasion is limited to be measured stronal invasion with a maximum depth of 5 mmb and no wider than 7 mm. IA1 Measured Invasion of stroma <_ 3 mm in depth and <_ 7 mm width. IA2 Measure invasion od stroma > 3 mm and <5 mm in depthband <_ mm width. |
IB | Clinical lesions confirmed to the cervix, or preclinical lesions greater than stage IA. IB 1 : Clinical lessons no greater than 4 cm in size. IB 2 : Clicnical lessons > 4 cm in size |
II | The carcinoma extends boy and the uterus, but has not extended on the pelvic wall or to the lower third of vagina. |
IIA | Involvement of up to the upper 2/3 of the vargina. No obvious parametrial involvement. IIA 1 : Clinically visible lesion <_ cm IIA 2 : Clinically visible lesion > 4 cm |
IIB | Obvious parametrial involvement but not onto the pelvic sidewall. |
III | The carcinomas has extendended on t the pelvic sidewall. On rectal examination there is no cancer-free space between the tumor and pelvic sidewall. The tumor involves the lower third of the vagina. All cases of hydronephrsis or non-functioning kidney should be included unless they are known to due to other causes. |
IIIA | Involvement of the lower vagina but no extension onto pelvic sidewall. |
IIIB | Extension onto the pelvic sidewall, or hydronephrosis non- functioning kidney. |
IV | The carcinoma has extended beyond the true pelvic or has clinically involved the mucosa of the bladder and or rectum. |
IVA | Spread to adjascent pelvic organs |
IVB | Spread to distant organs. |
Ca Cervix can be managed
* Refer patient to higher center for further management.
• SURGERY
• RADIATION
• CHEMOTHERAPY
• A COMBINATION OF ABOVE
General Treatment Scheme for Invasive Cervical Carcinoma
• Stage IA1 Simple hysterectomy, abdominal or vaginal, or cervical conization Stages
• 1A2,b hA, I131, and nonbulky hA Radical (class Ill) hysterectomy or trachelectomy, bilateral pelvic lymphadenectomy with postoperative irradiation, plus or minus concurrent chemotherapy in selected high-risk patients
• Stages 1132 and bulky hA Full external and intracavitary pelvic irradiation with concurrent chemotherapy (extrafascial hysterectomy) or radical abdominal hysterectomy and pelvic
(periaortic lymphadenectomy)
• Stages IIB to IVA Full external and intracavitary pelvic irradiation with concurrent chemotherapy Stage IVB Palliative chemotherapy
References
No references available