2. Epidemiology
• Cervical cancer is the fourth most common cancer in women
• Seventh overall
• Majority (around 85%) of the global burden occurs in the less
developed regions, where it accounts for almost 12% of all
female cancers.
• High-risk regions include Eastern Africa (42.7), Melanesia
(33.3), Southern (31.5) and Middle (30.6) Africa.
• Rates are lowest in Australia/New Zealand (5.5) and Western
Asia (4.4).
GLOBOCAN 2012
3. Epidemiology
• There were an estimated 266,000 deaths from cervical cancer
worldwide in 2012.
• 7.5% of all female cancer deaths.
• Almost nine out of ten (87%) cervical cancer deaths occur in
the less developed regions.
GLOBOCAN 2012
4.
5.
6. Trends in incidence of cervical cancer in selected countries: age-
standardised rate (W) per 100,000
7.
8. Indian data
• Cervical cancer is most common cancer in Indian women
• In India, cervical cancer had increased from 0.11 million in
2000 to 0.16 million in 20141
• Over 80% of the cervical cancer present at a advanced stage
and annually around 80,000 deaths are reported in India 2 .
1.Sankaranarayanan R, Black RB, Parkin DM, Cancer survival in developing countries. Editors-Lyon; IARC Press; 1998 (IARC
Scientific Publications #145)
Ferlay J, Shin HR, Bray F, Forman D, Mathers CD, Parkin D. Cancer Incidence and Mortality Worldwide GLOBOCAN 2008,: IARC
cancerBase No. 10. Lyon, France: International Agency for Research on Cancer; Year. Available at: http://globocan.iarc.fr. 2010
9. • India, the second most populous country in the world,
accounts for 27% (77,100) of the total cervical cancer deaths1
• This disproportionately high burden of cervical cancer in
developing countries (including India)
• Largely due to a lack of screening that allows detection of
precancerous and early stage cervical cancer 1,2.
1.Mathew A, George PS. Trends in incidence and mortality rates of squamous cell carcinoma and adenocarcinoma of cervix–
worldwide. Asian Pac J Cancer Prev. 2009; 10:645-650.
2. Vizcaino AP, Moreno V, Bosch FX, et al. International trends in incidence of cervical cancer: II. Squamous-cell carcinoma. Int J
Cancer. 2000; 86:429-435
12. CERVIX
The cervix is composed of two regions;
the ectocervix and the endocervical
canal.
• The ectocervix is the portion of the
cervix that projects into the vagina.
• The cervix opens onto the vagina
through an orifice called the external
os.
• It is lined by stratified squamous non-
keratinized epithelium.
The overlapping border between the endocervix and ectocervix is called
the transformation zone.
13.
14.
15.
16. • The endocervix - proximal part of
the cervix.
• It is a luminal cavity between the
external os and the internal os.
• Fusiform shaped
• The upper limit - internal os or
isthmus.
• Transition from the endocervix to
the endometrium (uterine cavity)
• simple columnar epithelium that
secretes mucus.
17.
18. The squamo-columnar junction (SCJ)
• The junction between the squamous epithelium and the columnar
epithelium.
• Its location on the cervix is variable.
• The SCJ is the result of a continuous remodeling process resulting
from uterine growth, cervical enlargement and hormonal status.
• During this process the original SCJ everts along with large portions
of columnar epithelium from their initial position onto the
ectocervix.
19.
20. TZ
• Transformation zone (TZ):
• Area between the original SCJ and the new SCJ where the
columnar epithelium (ectropion) has been replaced and/or is
being replaced by the new metaplastic squamous epithelium.
• The TZ may be either wide or narrow depending on age,
parity, prior infections and exposure to female hormones.
21.
22. Cervix Blood suppy
• The blood supply to the
uterus is via the uterine
artery.
• Venous drainage is via a
plexus in the broad
ligament that drains into
the uterine veins.
• Lymphatic drainage of the
uterus is via the iliac,
sacral, aortic and inguinal
lymph nodes.
24. • Three channels facilitate lymphatic drainage from the
cervix.[10]
• The anterior and lateral cervix drains to nodes along the
uterine arteries, travelling along the cardinal ligaments at the
base of the broad ligament >> external iliac lymph
nodes >> paraaortic lymph nodes.
• The posterior and lateral cervix drains along the uterine
arteries to the internal iliac lymph nodes >> paraaortic lymph
nodes,
• Posterior section of the cervix drains to the obturator and
presacral lymph nodes.[2][9][10]
25. Cervix Nerve supply
• The pelvic splanchnic nerves, emerging as S2–S3, transmit the
sensation of pain from the cervix to the brain.[4]
• These nerves travel along the uterosacral ligaments, which
pass from the uterus to the anterior sacrum.[8]
26. CERVIX FUNCTIONS
• Cervical glands secrete mucus.
• Mucus is thick - menstrual cycle, pregnancy, the and stops
sperm from entering the uterus.
• The thick mucus protect the uterus and the upper female
reproductive organs from harmful bacteria.
• During ovulation mucus becomes thinner - allows sperm to
pass through the cervix into the uterus.
• Aids in menstruation -Passage
• During childbirth, the cervix widens, or dilates, allowing the
baby to pass through the birth canal.
27. RISK FACTORS
• Patient related
• Life style
• Smoking is associated with increased risk due to accumulation
of carcinogens in the cervical mucus.
• Oral contraceptive use is controversial
28. • Environmental
• Infectious exposure: HPV
• Environmental exposure: Smoking (active and passive
exposure)
• DES exposure in utero is associated with for clear cell
adenocarcinoma
29. A. AGE: It affects relatively young women with incidence increasing
rapidly from the age of 25 to 45.
B. GENITAL WARTS: Past/ present occurrence of clinical genital warts is
an important risk factor.
C. MARITAL STATUS: The disease is linked with sexual intercourse.
D. EARLY MARRIAGE: Early marriage, early coitus, early childbearing
and repeated childbirth have been associated with increasing risk.
E. ORAL CONTRACEPTIVE PILLS: There is renewed concern about the
possible relationship between pill use and the development of invasive
cervical cancer. A recent World Health Organization (WHO) study
finds an increased risk with increased duration of pill use and with
the use of oral contraceptives high in oestrogen.
F. SOCIO-ECONOMIC CLASS: It is more common in lower
socioeconomic groups reflecting probably poor genital hygiene,
30. HPV
• >90% of cervical cancers are related to the presence of human
papilloma virus (HPV) and are contracted via sexual intercourse.6
• HPV is a small, double-stranded DNA virus;
• HPV 16 and 18,
• HPV 31, 33,35, 39, 45, 51, 52, 56, and 58 7.
• Life style:
• Early age of first sexual intercourse,
• Multiple sexual partners,
• Male partner with multiple sexual partners
• exposure to sexually transmitted diseases (gonorrhea, chlamydia,
HSV II, HIV)
• high parity
32. • Peak age - 25 to 35 years,
• <15% of exposed women develop persistent infection that
results in dysplasia,9
• majority of women clear the infection within 2 years.10
• Cervical cancer may develop 10 to 20 years after initial
exposure to HPV.
33. HPV Vaccination
• The quadrivalent human papillomavirus recombinant vaccine
for HPV types 6, 11, 16, and 18, first approved in the United
States in 2006 for girls and women ages 9 to 26 years.
• now available for boys ages 9 to 26 years, with the goal of
eradicating HPV related gynecologic, penile, anal, and
oropharyngeal cancers.
• A second vaccine with strong immunogenicity to HPV types 16
and 18, approved for girls 9 to 25 years old, is more frequently
• administered in Europe.
• its development is a major advance in the prevention of
cancer,
• vaccine implementation has been hindered worldwide by cost
and access.
34. Pathology
• Squamous cell carcinoma (SCC) accounts for 85% of all
cervical cancers.
• Non squamous histologies - Adenocarcinoma,
- Adenosquamous
- Undifferentiated
• Less common (15%)
• Associated with poorer prognosis.
35. Natural history - microscopic
• Squamous cell carcinoma at
the squamous columnar
junction
• stepwise progression from
normal to higher levels of
dysplasia.
• (CIN) type 1, 60% have
regression of the lesion, and
of those with CIN2, 40%
regress.
• Higher levels of dysplasia -
progress to cancer
• progression typically takes 10
to 20 years,31,32
36. Natural history - Spread
Local extension
Parametria,
Uterosacral ligaments,
Vesicovaginal space, and
Perirectal space;
Vagina
Ovarian spread
Regional lymphnode spreadDistant metastasis
uncommon in the absence
of extensive local or lymph node
involvement
Most common distant
metastatic sites are lung, liver,
and bone
39. Lymph node
group
Stage
I II III
Pelvic LN 15% 30% 50%
Para-aortic LN 5% 20% 30%
Involvement of lymph node groups (in %) by stage
40. SCREENING – PAP SMEAR
• ACOG-2009
• begin at age 21 years and
• continue every 2 years until age 30 years
• if there are three normal consecutive Pap smears and no history of
CIN2, CIN3, DES exposure, or HIV infection and the woman is not
otherwise immunocompromised, screening should be every 3 years
• Hysterectomy+ No h/o HSIL -discontinue testing
• Pap smear + HPV DNA - Low-risk women older than age 30 years.
• If negative, rescreening is not required sooner than 3 years.
41. SCREENING – PAP SMEAR
• H/O treatment for CIN2 or CIN3 - annual screening x 20 years.
• Those who have had a hysterectomy and a history of CIN2/
CIN3 should continue to undergo screening with annual pelvic
exams.
43. Clinical Presentation
• Signs
• GPE – Pallor, Aniorexic, Lowe limb edema
• P/A- Palpable mass in the lower abdomen, Hepatomegaly,
Inguinal nodes
• Local examination -
44.
45.
46.
47. Diagnostic workup
Tissue diagnosis
• Diagnosis is made by Pap smear and/or biopsy
• Normal Pap smear in the presence of visible abnormality does
not exclude tumor
• Biopsy, endocervical curettage, and if negative, cold-knife
conization must be performed
Lab:
• CBC, LFT, KFT, Coagulation profile
• Viral Markers
• Urinalysis
48. Diagnostic workup
Radiology:
• Chest x-ray
• CT or MRI of abdomen and pelvis
• PET Scan
Procedures :
• Exam under anesthesia
• Cystoscopy,
• Proctoscopy,
• ureteral stent placement as indicated
49. CT Scan
• CT is equally effective for evaluation of extrauterine spread of
the disease
• A significant number of clinicians prefer CT for the evaluation
of oncologic patients, due to its wide availability[17]
• CT accuracy for overall cervical cancer staging, ranges from
32%-80%.
• cannot discriminate between normal cervical stroma and
cancerous tissue
Thomeer MG, Gerestein C, Spronk S, van Doorn HC, van der Ham E, Hunink MG. Clinical examination versus magnetic resonance imaging in the pretreatment staging of cervical carcinoma:
systematic review and meta-analysis. Eur Radiol 2013; 23: 2005-2018 [PMID: 23455762 DOI: 10.1007/s00330-013-2783-4]
Subak LL, Hricak H, Powell CB, Azizi L, Stern JL. Cervical carcinoma: computed tomography and magnetic resonance imaging for preoperative staging. Obstet Gynecol 1995; 86: 43-50 [PMID:
7784021 DOI: 10.1016/0029-7844(95)00109-5]
50. • Performs poorly, therefore, in assessing local spread with
lower than 58% PPV for detection of early parametrial
invasion[1,2]
• Currently, staging with CT is limited to patients with clinical
evidence of advanced disease or contraindications to MRI.
1.Subak LL, Hricak H, Powell CB, Azizi L, Stern JL. Cervical carcinoma: computed tomography and magnetic resonance imaging for preoperative staging. Obstet Gynecol 1995; 86: 43-50
[PMID: 7784021 DOI: 10.1016/0029-7844(95)00109-5]
2. Ho CM, Chien TY, Jeng CM, Tsang YM, Shih BY, Chang SC. Staging of cervical cancer: comparison between magnetic resonance imaging, computed tomography and pelvic examination
under anesthesia. J Formos Med Assoc 1992; 91: 982-990 [PMID: 1362678]
51. MRI Scan
• MRI is the preferred imaging modality for evaluating local extent of
cervical cancer due to its high contrast resolution which enables
differentiation between cancerous and normal tissues[5,26,27].
• MRΙ is primarily used for the evaluation of tumor morphology and
local extent
• It accurately evaluates tumor features with a significant prognostic
value, like size, endocervical growth, parametrial infiltration and
pelvic side wall or adjacent organ (bladder, rectum) involvement.
• Reported MRI accuracy values for determining tumor stage
(operable vs advanced disease) range from 75%-96%[5,21,26,28-
30].
Sala E, Rockall AG, Freeman SJ, Mitchell DG, Reinhold C. The added role of MR imaging in treatment stratification of patients with gynecologic malignancies:
what the radiologist needs to know. Radiology 2013; 266: 717-740 [PMID: 23431227 DOI: 10.1148/ radiol.12120315]
52. MRI Scan
• Clinical staging of early cervical cancer and assessment of
important prognostic factors significantly improves when MRI
information is added to the clinical data;
• MRI helps select surgical candidates among patients with
cervical cancer, because it has a high negative predictive value
(94%-100%) for parametrial involvement.
• Also, when findings of clinical examination are unclear or
when it cannot be performed due to patient obesity or
discomfort, MRI may be used for treatment planning.
Hricak H, Gatsonis C, Coakley FV, Snyder B, Reinhold C, Schwartz LH, Woodward PJ, Pannu HK, Amendola M, Mitchell DG. Early invasive cervical
cancer: CT and MR imaging in preoperative evaluation - ACRIN/GOG comparative study of diagnostic performance and interobserver variability.
Radiology 2007; 245: 491-498 [PMID: 17940305 DOI: 10.1148/radiol.2452061983]
Bourgioti C, Chatoupis K, Rodolakis A, Antoniou A, Tzavara C, Koutoulidis V, Moulopoulos LA. Incremental prognostic value of MRI in the staging of
early cervical cancer: a prospective study and review of the literature. Clin Imaging 2016; 40: 72-78 [PMID: 26459788 DOI:
10.1016/j.clinimag.2015.09.012]
53. PET Scan
• PETCT shows high diagnostic performance for the detection of
tumor relapse and metastatic lymph nodes
• (PET/CT) may detect small FDGavid tumors 7 mm or less[1]
• Hybrid imaging (PET-CT or PET-MRI) is superior to conventional
cross- sectional techniques for identifying metastatic lymph nodes,
with excellent diagnostic accuracy, ranging from 85%-99%[2,3]
• However, its role in the initial evaluation of cervical cancer has not
been established. Accuracy of PET-CT for local staging of cervical
cancer is moderate (53.3%). PET-MRI may be promising for the
assessment of primary tumor, with sensitivity and specificity values
over 90%
1.Mirpour S, Mhlanga JC, Logeswaran P, Russo G, Mercier G, Subramaniam RM. The role of PET/CT in the management of cervical cancer. AJR Am J
Roentgenol 2013; 201: W192-W205 [PMID: 23883234 DOI: 10.2214/AJR.12.9830]
2. Choi HJ, Ju W, Myung SK, Kim Y. Diagnostic performance of computer tomography, magnetic resonance imaging, and positron emission
tomography or positron emission tomography/computer tomography for detection of metastatic lymph nodes in patients with cervical cancer: meta-
analysis. Cancer Sci 2010; 101: 1471-1479 [PMID: 20298252 DOI: 10.1111/j.1349-7006.2010.01532.x]
3.Grueneisen J, Schaarschmidt BM, Heubner M, Aktas B, Kinner S, Forsting M, Lauenstein T, Ruhlmann V, Umutlu L. Integrated PET/MRI for whole-
body staging of patients with primary cervical cancer: preliminary results. Eur J Nucl Med Mol Imaging 2015; 42: 1814-1824 [PMID: 26199113 DOI:
10.1007/s00259-015-3131-5]
