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Cervical Cancer Prof. M.C.Bansal MBBS,MS,MICOG,FICOG Professor OBGY Ex-Principal & Controller Jhalawar Medical College & HospitalMahatma Gandhi Medical College, Jaipur.
Epidemiology and Risk Factors• Preventable disease because it has a long pre-invasive state, cervical cytology screening programs are currently available, and the treatment of pre-invasive lesions is effective.• It is estimated that 30% cervical cancer cases will occur in women who have never had a Pap test. In developing countries, this percentage approaches 60%.• The worldwide incidence of invasive disease is decreasing, and cervical cancer is being diagnosed earlier, leading to better survival rates (1,3).• The mean age for cervical cancer in the United States is 47 years, and the distribution of cases is biomodal, with peaks at 35 to 39 years and 60 to 64 years of age.
Risk Factors• Young age at first intercourse (<16years), multiple sexual partners, cigarette smoking, race, high parity, and lower socioeconomic status.• Oral contraceptives may increase the incidence.• Many of these risk factors are linked to sexual activity and exposure to STD.• Infection with human papillomavirus (HPV) has now been determined to be the causal agent.• The role of human immunodeficiency virus (HIV) in Ca Cx is thought to be mediated through immune suppression.
Mechanism of HPV• HPV infection has been detected in up to 99% of women with squamous Ca Cx.• There are more than 100 different types of HPV, and more than 30 of which can affect the lower genital tract.• There are 14 high-risk HPV subtypes; two of the high- risk subtypes, 16 and 18, are found in up to 62% of Ca Cx.• The mechanism by which HPV affects cellular growth and differentiation is through the interaction of viral E6 and E7 proteins with tumor suppressor genes p53 and Rb respectively.
Mechanism of HPV cont….• Inhibition of P53 prevents cell cycle arrest and cellular apoptosis, which normally occurs when damaged DNA is present, whereas inhibition of Rb disrupts transcription factor E2F, resulting in unregulated cellular proliferation.• Both steps are essential for the malignant transformation of cervical epithelial cells.
EvaluationSymptoms –1. Vaginal bleeding is the most common symptoms occurring in patients with Ca Cx.2. Irregular or a cyclic, intermenstrual bleeding or post menopausal bleeding.3. Post coital, post examination bleeding.4. Blood stand foul smelling vaginal discharge.5. Weight loss, or obstructive uropathy.6. In asymptomatic women Ca Cx is identified through evaluation of abnormal cytological screening test.
Signs – Ca Cx• PS & PV Examination – A. Cauliflower exophytic growth (80%) which is friable, fixed, penitrable with probe, indurated and it bleeds on touch. B. Ulcerative growth (20%) which has indurated base and bleeds on touch. C. Flat inddrated area.PR – Enlarge bulky cervix is felt. Induration of secral ligaments can be appreciated. Rectal mucosa may be free involve by ca growth.
Colposcopy findings of Invasive Ca Cx• Colposcopic findings that suggest invasion are i. abnormal blood vessels, ii. Irregular surface contour with loss of surface epithelium, and iii. Color tone change.• Colposcopically directed biopsies may permit the diagnosis of frank invasion and thus avoid the need for diagnostic cone biopsy.
Colposcopy findings of Invasive Ca Cx cont…• Abnormal Blood Vessels-• Abnormal vessels may be looped, branched, or reticular. Abnormal looped vessels are the most common colposcopic finding and arise from the punctated and mosaic vessels present in cervical intraepithelial neoplasia (CIN).• Abnormal reticular vessels represent the terminal capillaries of the cervical epithelium.
Colposcopy findings of Invasive Ca Cx cont…• Irregular Surface Contour-The surface epithelium ulcerates as the cells lose intercellular cohesiveness secondary to loos of desmosomes.Irregular contour also may occur as a result of papillary characteristics of the lesion.
Colposcopy findings of Invasive Ca Cx cont…• Color Tone – Color tone may change as a result of increasing vascularity, surface epithelial necrosis, and in some cases, production of keratin. The color tone is yellow-orange rather than the expected pink of intact squamous epithelium or the red of the endocervical epithelium.• Adenocarcinoma – Adenocarcinoma of the cervix does not have a specific colposcopic appearance. Adenocarcinomas tend to develop within the endocervix, endocervical curettage is required as part of the colposcopic examination.
Histologic Appearance of Invasion• Depth of invasion is a significant predictor for the development of pelvic lymph node metastasis and tumor recurrence.• Although lesions that have invaded 3 mm or less rarely metastasize, patients in whom lesions invade between 3 to 5 mm have positive pelvic lymph nodes in 3% to 8% of cases.
FIGO-Staging• Preinvasive Carcinoma- – Stage 0:- Carcinoma in situ, intraepithelial carcinoma (Cases of stage 0 should be included in any therapeutic statistic). • Invasive Carcinoma- – Stage 1:- Carcinoma strictly confined to the cervix (extension to the corpus should be disregarded). – Stage 1a:- Preclinical carcinomas of the cervix, that is, those diagnosed only by microscopy. – Stage 1a1:- Lesion with ≤ 3 mm invasion. – Stage 1a2:- Lesions detected microscopically that can be measured. The upper limit of the measurement should show a depth of invasion of > 3-56 mm taken from the base of the epithelium, either surface or glandular, from which it originates, and a second dimension, the horizontal spread, must not exceed 7 mm. larger lesions should be staged as 1b. – Stage 1b:- Lesions invasive > 5 mm. – Stage 1b1:- Lesion ≤ 4 cm. – Stage 1b2:- Lesions > 4 cm.
Figo-Staging cont…• Stage 2:- The carcinoma extends beyond the cervix but has not extended onto the wall. The carcinoma involves the vagina, but not the lower one third.– Stage 2a:- No obvious parametrial involvement.– Stage 2b:- obvious parametrial involvement.• Stage 3:- The Carcinoma has extended onto the pelvic wall. On rectal examination, there is no cancer-free space between the tumor and the pelvic wall. The tumor involves the lower one third of the vagina. All cases with hydronephrosis or nonfunctioning kidney.– Stage 3a:- No extension to the pelvic wall.– Stage 3b:- Extension onto the pelvic wall and/or hydronephrosis or nonfunctioning kidney.• Stage 4:- The carcinoma has extended beyond the true pelvis or has clinically involved the mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allotted to stage IV. – Stage 4a:- Spread to the growth to adjacent organs – Stage 4b:- Spread to distant organs.
Pathology• Squamous Cell Carcinoma:- Invasive squamous cell carcinoma is the most common variety of invasive cancer in the cervix. (80% incidence). large cell keratinizing, large cell nonkeratinizing, and small cell types. The category of small cell carcinoma includes poorly differentiated squamous cell carcinoma and small cell anaplastic carcinoma. It is more aggressive and carries poor progonosis. Verrucous carcinoma and papillary (transitional) carcinoma are reared variants of squamous cell carcinoma.
Adenocarcinoma• In recent years, It has increasing trends, reported in 20 to 30 years of ages.• Newer reports show a proportion as high as 18.5% to 27% as compared to 5% in older reports.• Adenocarcinoma of the cervix is managed in the same a manner to that used for squamous cell carcinoma.• About 80% of cervical adenocarcinomas are made up predominantly of cells of the endocervical type with mucin production.• The remaining tumors are populated by endometrioid cells, clear cells, intestinal cells or a mixture of more than one cell type.
Other Varities of Ca Malignancy• Adenosquamous Carcinoma• Sarcoma – Embryonal rhabdomyosarcoma, Leiomyosarcomas and mixed mesodermal tumors and cervical adenosarcoma.• Malignant Melanoma• Neuroendocrine CarcinomaNote: They are the rarest varities
Patterns of Spread Ca Cx• Ca Cx spreads by 1. direct invasion into the cervical stroma, corpus, vagina, and parametrium; 2. Lymphatic metastasis; 3. Blood-borne metastasis; 4. Intraperitioneal implantation.