3. Epidemiology
• Cancer of the cervix uteri is the second most
common cancer among women worldwide
BUT
• for Tanzania is the leading type of cancer in
women and the commonest cause of cancer
related deaths in this country.
4. Burden in Tanzania
• Tanzania has a population of 10.97 millions women ages 15
years and older who are at risk of developing cervical cancer.
• Current estimates indicate that every year 6241 women are
diagnosed with cervical cancer and 4355 die from the disease.
• Cervical cancer ranks as the 1st most frequent cancer among
women in Tanzania, and the 1st most frequent cancer among
women between 15 and 44 years of age
5. Projections
• Projected number of new cervical cancer cases in
2025* is estimated to increases to 10257
• Projected number of cervical cancer deaths in
2025* is estimated to increase to 7173
Cervical cancer is on the increase
6. Pathogenesis
Cancer of the cervix has been regarded as a preventable
cancer because;
1. Known etiology. (HPV)
2. It has a long pre-invasive state.
3. Cervical cytological screening programs are available
4. Treatment of pre-invasive lesions is effective.
7. • Invasive cervical cancers are usually preceded by a
long phase of preinvasive disease.
• This is characterized microscopically as a
spectrum of events progressing from cellular
atypia to various grades of dysplasia or cervical
intraepithelial neoplasia (CIN) before progression
to invasive carcinoma
8. A good knowledge of the etiology, pathophysiology
and natural history of these pre-invasive conditions
provides a strong basis both for visual testing and
for colposcopic diagnosis and understanding the
principles of treatment of these lesions.
9. • CIN and cancer of cervix is a single, continuous disease
process by which normal epithelium evolves into
epithelial precursor lesions and on to invasive cancer.
• Precancerous lesions are usually discovered by a
screening test, the Papanicolaou or "pap" smear
10.
11. Grades of CIN
(pre-invasive cancer)
CIN1 (Grade I)
• The least risky type, represents only mild dysplasia, or
abnormal cell growth and corresponds to a low grade
squamous intraepithelial lesion (LGSIL)..
• It is confined to the basal 1/3 of the epithelium.
• This corresponds to infection with HPV, and mostly will
be cleared by immune response in a year or so, though
can take several years to clear.
12. • as well as CIN III, correspond to high
grade squamous intraepithelial
lesions (HGSIL). CIN2 represents
moderate dysplasia, and is confined
to the basal 2/3 of the epithelium.
CIN2 (Grade II)
13. CIN3 (Grade III):
In this lesion, severe dysplasia spans
greater than 2/3 of the entire epithelium,
and may involve the full thickness. This
lesion may sometimes also be referred to
as cervical carcinoma in situ.
14. Disease Progression
The course of a specific lesion is influenced by;
1. Inciting HPV type.
2. Patients immune status
3. Smoking habits.
4. Time/duration
15. Disease Progression
CIN I CIN II CIN III
Regression to normal 60% 40% 30%
Persistence 30% 35% 48%
Progression to CIN III 10% 20% -
Progression to cancer <1% 5% 22%
16. Disease Progression
• However most CIN spontaneously regress.
• Progression to cancer typically takes 15 (3 to 40) years
• Also, evidence suggests that cancer can occur without
first detectably progressing through these stages and
that a high grade intraepithelial neoplasia can occur
without first existing as a lower grade.
17. Etiology
Epidemiological studies have identified a number of risk factors
that contribute to the development of cervical cancer
precursors and cervical cancer
• infection with certain oncogenic types of human
papillomaviruses (HPV),
• sexual intercourse at an early age,
• multiple sexual partners
18. • long-term oral contraceptive use,
• tobacco smoking
• low socioeconomic status
• multiparity
• micronutrient deficiency
• diet deficient in vegetables and fruits.
19. • Persistent infection with one or more of the
oncogenic types of HPV is considered to be a
necessary cause for cervical neoplasia.
• HPV infection is transmitted through sexual contact
and the risk factors therefore are closely related to
sexual behaviour (e.g., lifetime number of sexual
partners, sexual intercourse at an early age).
20. • HPV infection is believed to start in the basal
cells or parabasal cells of the metaplastic
epithelium
• Typically the disease starts at the squamo-
columna junction or transformation zone
• If the infection persists, integration of viral
genome into the host cellular genome occur.
21. • The normal differentiation and maturation of the immature
squamous metaplastic into the mature squamous
metaplastic epithelium may be disrupted as a result of
expression of E6/E7 viral oncoproteins and the loss of
normal growth control
• E6 and E7 have the ability to complex with the tumor
suppressor genes p53 and Rb, respectively
• This may then lead to development of abnormal dysplastic
epithelium
22. • If the neoplastic process continues uninterrupted, the
early low-grade lesions may eventually involve the full
thickness of the epithelium.
• Subsequently the disease may traverse the basement
membrane and become invasive cancer, extending to
surrounding tissues and organs
23. • Despite women’s frequent exposure to HPV,
development of cervical neoplasia is
uncommon
• Most cervical abnormalities caused by HPV
infection are unlikely to progress to high-
grade CIN or cervical cancer, as most of
them regress by themselves
25. Etiology
The long time frame between initial infection and overt
disease indicates that several cofactors (e.g., genetic
differences, hormonal effects, micronutrient deficiencies,
smoking, or chronic inflammation) may be necessary for
disease progression.
• Immune system?
26. There are > 70 HPV subtypes, half of which infect
the ano-genital epithelium based on their
malignant potential, HPV subtypes are classified
as
• high risk,
• intermediate risk and
• low risk subtypes
27. • Low risk HPV (6,11,42,43,55) are associated with
condylomata and low grade pre-malignant
lesions of the cervix
• Intermediate risk HPV (33,35,51,520 are
associated with high grade lesion of the cervix.
• High risk HPV (16,18,31,39,45,57,58,59,68) are
associated with high grade lesions and invasive
cancer of the cervix.
28. • Cigarette smoking and HPV act synergistically on the
development of CIN.
• Cigarette smoking is associated with two to four fold
increase in relative risk for development of cervical
Cancer.
• Cigarette smoke carcinogens have been found to accumulate
locally in the cervical mucus and cumulative exposure as
measured by pack-year smoked is related to the risk of
developing CIN or carcinoma insitu.
• Incidence of cervical neoplasia is increased in HIV
infected women
29. Treatment of pre-invasive lesions (CIN)
• Cryotherapy
Nitrous oxide or carbon dioxide is used as the refrigerant for a
super-cooled probe
The cryoprobe is positioned on the ectocervix where it must cover
the entire lesion, which at times is not easily achieved. It is then
activated until blanching of the cervix extends at least 7 mm
beyond the probe in all directions in order to assure that freezing
extends beyond the depth of the crypts of the glands into which
the dysplasia might be extending.
30. Carbon Dioxide Laser
The laser destroys tissue with a very narrow zone of
injury around the treated tissue, and is therefore both
precise and flexible.
The tissue is vaporized to a depth of at least 7 mm to
assure that the bases of the deepest glands are
destroyed
31. • Loop Electrosurgical Excision Procedure (LEEP)
LEEP uses a small, fine, wire loop attached to an
electrosurgical generator to excise the tissue of interest.
Various sizes of wire loop are available
Following LEEP excision of the transformation zone,
frequently an additional narrow endocervical specimen is
removed to allow for histologic evaluation while avoiding
excessive damage to the cervical stroma
32. • Cold Knife Conization
Cold knife conization of the cervix refers to the excision of a
cone-shaped portion of the cervix using a scalpel. This
technique can be individualized to accommodate the
cervical anatomy and the size and shape of the lesion
Cervical cone biopsy is generally done in the operating
room under local or general anesthesia. Complications
include bleeding, infection, cervical stenosis, and cervical
incompetence
34. CERVICAL CANCER:
Invasive cancer
• Age of incidence: Used to be a disease of old women but
nowadays the age of onset has decreased significantly.
• The average age at diagnosis of patients with cervical cancer is 51
years. However, the disease can occur in the second decade of life
• 75% decrease in the incidence of cervical cancer in developed
countries following the implementation of population-based
screening programs and treatment of preinvasive disease
35. • But the disease is on the increase in developing
countries
No active screening programs
Few treatment option
• Most patients In sub-Saharan Countries and
Tanzania is number 2 after Zambia
37. Symptoms and Signs
• Abnormal vaginal bleeding is the most common symptom of
invasive cancer and may take the form of a blood-stained
leukorrheal discharge, scant spotting, or frank bleeding.
Leukorrhea, usually sanguineous or purulent, odorous, and
nonpruritic, is frequently present.
• A history of postcoital/contact bleeding may be elicited on
specific questioning.
38. • Pelvic pain, often unilateral and radiating to the hip or
thigh, is a manifestation of advanced disease.
• Also, as is the involuntary loss of urine or feces through
the vagina, a sign of fistula formation.
• Weakness, weight loss, and anemia are characteristic of
the late stages of the disease, although acute blood loss
and anemia may occur in an ulcerating stage I lesion.
39. Physical examination
• Speculum examination: Infiltrative cancer produces
enlargement, irregularity, and a firm consistency of the cervix
and eventually of the adjacent parametria.
• The growth pattern can be endophytic, leading to a barrel-
shaped enlargement of the cervix, or exophytic, where the
lesion generally appears as a friable, bleeding, cauliflower
like lesion of the portio vaginalis.
40. • Ulceration on the cervix may be the
primary manifestation of invasive
carcinoma;
• With further progression of the disease,
the ulcer becomes deeper and necrotic
41. • The adjacent vaginal fornices may become
involved next. Eventually, extensive
parametrial involvement by the infiltrative
process may produce a nodular thickening of
the uterosacral and cardinal ligaments with
resultant loss of mobility and fixation of the
cervix.
46. Cervical cancer staging
• Stage 0 (CIN III) = carcinoma in situ
• Stage 1A = Microinvasive carcinoma
• Stage 1B = cancer confined to the cervix
• Stage 2A = cancer extend to the upper third of the
vagina
• Stage 2B = cancer extend to the parametrium but not to
the pelvic side walls
47.
48. • Stage 3A = cancer involving the lower third of the
vagina
• Stage 3B = cancer extends to the pelvic side walls
(often obstructing the ureter)
• Stage 4A = cancer involving the bladder and/or
rectum
• Stage 4B = Distant metastasis
49. Treatment of cervical cancer
• Surgical approach: For very early cervical cancer (1A)
Hysterectomy plus lymph node dissection
• Main stay is Radiotherapy with chemotherapy (Cisplatin IV)
External beam followed by intracavitary
50. PREVENTION OF CERVICAL CANCER
1. Cervical cancer screening to detect premalignant
conditions
Visual inspection of the cervix (Speculum) with
acetic acid or Iodine = Acetowhite changes
Pap smears
Colposcopy and Biopsy
51. 2. Vaccine for HPV to all women before they are infected
(Before they start sexual activity)
Young girls are the major target but any woman 10-50 can
receive the vaccine
3. Sexual behavior
Late onset of sex
Number and behavior of sexual partners
Male circumscion
