Carcinoma of the cervix from introduction to conclusion

1. 1
CERVICAL CANCER
BY
DR. AYODELE, NOSRULLAH S
FMC, BIRNIN KEBBI

2. OUTLINE
 INTRODUCTION
 EPIDEMIOLOGY
 AETIOLOGY
 PATHOGENESIS
 CLINICAL PRESENTATION
 INVESTIGATIONS
 COMPLICATIONS
 TREATMENT
 PREVENTION
 SUMMARY
 CONCLUSION
 REFERENCES 2

3. INTRODUCTION
 Cervical cancer is the most common
gynecologic cancer in women globallly 1,2
 It ranks third among all malignancies for
women
 More common in the younger population of
women
 Until recently, ca cervix was linked with many
viral infections as the cause, e.g. CMV, HSV II
3

4. INTRODUCTION
 Human Papilloma Virus (HPV) is now
considered a sexually transmitted disease
with particular types being highly oncogenic
as cause of ca cervix
 More than 150 types of HPV have been
described 3
 Screening for HPV is very important in the
prevention and management of ca cervix
4

5. INTRODUCTION
 Screening is usually done with Pap smear
sampling and typically begins in young
adulthood
 Recently, highly specific HPV DNA tests have
been developed for the detection of HPV in
cervical /vaginal preparations e.g.
 Polymerase Chain Reaction tests
 Hybrid II Capture tests
5

6. INTRODUCTION
 Screening for precursor lesions of the cervix
has led to a marked reduction in cervical
cancer death rate by about 70%
 Other tests used in low resource settings
include
 Visual inspection with Lugol’s iodine (VILI)
 Visual inspection with acetic acid (VIA)
 Vaccines are currently available for prevention
6

7. EPIDEMIOLOGY
 Worldwide about 500,000 women acquire the
disease annually
 About 75-85% are from developing countries
 About 300,000 women die of the disease
annually
 Incidence has fallen considerably in Europe
and America due to
 Improved public health measures - the screening
procedures
 Lifestyle modification
 Pap smear screening 7

8. EPIDEMIOLOGY
 In Nigeria ca cervix ranks as the 2nd leading
cause of female cancer 7
 About 14,089 new cases are diagnosed
annually 7
 A 2012 study found the rate to be
17.1/100,000 women/year 7 (similar with
many other studies)
 About 8,240 cervical cancer deaths occur
annually in Nigeria (2nd leading cause of
cancer death in women) 7
8

9. AETIOLOGY
 The WHO in 1996 declared HPV as the major
cause of cancer of the cervix 2
 The WHO's International Agency for Research
on Cancer (IARC) has classified the HPV into
three groups 2
 carcinogenic (HPV types 16 and 18)
 probably carcinogenic (HPV types 31 and 33)
 possibly carcinogenic (other HPV types except 6
and 11)
9

10. AETIOLOGY
 The commonest strain is type 16, can be
retrieved in over 80% of ca cervix specimens
 Type 18 seen in a few cases and usually
affect the endocervical glands
 Other types involved in cervical changes
include but not limited to the following types:
 31, 33, 51, 53, 35 etc.
 In developing countries type 35 may be second to
type 16.
10

11. RISK FACTORS
 Lack of regular cervical screening
 High risk sexual behaviour
 Early coitarche (age at first coitus, <20yrs).
 Early marriage.
 Multiple child births (P2=2 fold, P7=4 fold)
 Frequent change of partners (promiscuity and
prostitution)
 Having a male partner with multiple sexual
partners
11

12. RISK FACTORS
 Family history
 Smoking (2-3x)
 Low socioeconomic status
 Long term COCP use (up to 4 fold)
 Low immunity
 Age :30-39 and 60-69 years, mean age=
51.4yrs
 Race – more in Africans
12

13. PATHOGENESIS
13

14. PATHOGENESIS
14

15. 15
PATHOGENESIS

16. PATHOGENESIS
 Like most other DNA viruses, HPV uses host
cell DNA polymerases to replicate its genome
and produce virions
 Highly virulent HPV produces two viral
oncoproteins, E6 and E7.
 The proteins inhibit p53, P21 and RB,
respectively – three potent tumor suppressors
that act to suppress the division of squamous
cells as they mature.
16

17. PATHOGENESIS
17

18. PATHOGENESIS
18

19. PATHOGENESIS
19

20. PATHOGENESIS
20

21. PATHOGENESIS
 Following tumorigenesis, the pattern of local
growth may be:
 Exophytic (cauliflower growth) - if a cancer arises
from the ectocervix,
 Endophytic (ulcerative growth) - if it arises from
the endocervical canal
 Tumour spread
 Direct extension
 Lymphatic
 Hematogenous (rare)
 Transceolomic 21

22. PATHOLOGY
 The main histological types of carcinoma of
the cervix are:
1. Squamous cell carcinoma (85- 90%).
 Large cell keratinising or non-keratinising
 Small cell
 Verrucous
2. Adeno-carcinoma (10- 15%)
 Typical endocervical
 Clear cell
 Endometroid
 Adenoid cystic (basaloid cylindroma)
 Adenoma malignum 22

23. PATHOLOGY
3. Mixed
 Adeno -squamous
 Glassy cell
4. Neuroendocrine
 Large cell neuroendocrine
 Small cell neuroendocrine
5. Other types
 lymphoma
 melanoma
 sarcoma
23

24. CLINICAL PRESENTATION
 May be asymptomatc or symptomatic
 Asymptomatic (early stages)
 discovered accidentally through screening
procedures or at Family Planning clinics
24

25. CLINICAL PRESENTATION
 Symptomatic
 Vaginal bleeding - irregular, intermenstrual, post-
coital, postmenopausal
 Vaginal discharge – copious, purulent, malodorous
 Cachexia
 Micturition symptoms – dysuria, frequency, urinary
incontinence from VVF
 Rectal symptoms – rectal pain
 Pedal oedema
 Pain – dyspareunia, low backache, deep pelvic
ache, sciatica. 25

26. DIFFERENTIAL DIAGNOSIS
 Ulcers of the cervix - tubercular and syphilitic
 Polyps - mucus, cervical, and fibroid polyps
 Endometrial carcinoma
26

27. GENERAL EXAMINATION
 Depending on the time of presentation.
 Early presentation - no specific findings
 Late presentation
 Anaemia
 Lymphadenopathy (inguinal, supraclavicular etc)
 Pedal oedema
 Ascites (rare)
27

28. PELVIC EXAMINATION
 Speculum vaginal examination – may reveal
lesions e.g.
 proliferative, cauliflower-like, vascular, friable
growth which bleed on touch
 ulcerative lesions with flat indurated areas
 Offensive vaginal smell
 Digital vaginal examination
 Feels firm with palpable nodules
 Bulky uterus due to pyometra
28

29. PELVIC EXAMINATION
 Rectal examination
 Nodules or masses, which indicate the possibility
of locally invasive disease
 Thickening and induration of uterosacral ligaments
 Parametrial nodularity
29

30. CLINICAL STAGING
 Done using FIGO/WHO/UICC system of
grading
 Early-stage disease refers to FIGO stages I
through IIA and advanced stage from IIB and
higher.
30

31. FIGO STAGING OF CERVICAL CANCER

33. CLINICAL STAGING
33

34. INVESTIGATIONS
 Investigations for diagnosis
 Pap Smear (if no obvious lesion)
 Colposcopy
 Cervical biopsy for histology (for obvious lesions)
 Pre-treatment investigations
 Full blood count
 Urinalysis
 E/U/Cr
 LFT
 Chest x-ray
34

35. INVESTIGATIONS
 ECG
 Abd-pelvic USS
 CT scan – evaluate liver, urinary tract,
bones,nodules sizes (≥1cm =positive)
 MRI – gives best images
 IVU – assesses renal function, ureter position
 Positron emission tomography - Lymph node
metastasis, distant metastasis
35

36. INVESTIGATIONS
 Cystoscopy - Tumor invasion into the bladder
 Proctoscopy - Tumor invasion into the rectum
 Examination under anesthesia - Extent of pelvic
tumor spread, clinical staging
36

37. PAP SMEAR CYTOLOGY
37

38. PAP SMEAR CYTOLOGY
38

39. HISTOLOGY OF CERVICAL CA
39

40. HISTOLOGY OF CERVICAL CA
40

41. HISTOLOGY OF CERVICAL CA
41
Squamous cell carcinoma, usual type.
This tumour is characterized by infiltrative
sheets and nest of cells without overt
keratinization
Squamous cell carcinoma. This tumour
exhibits overt keratinization either as
keratin pearls or as individual densely
keratinized cells

42. HISTOLOGY OF CERVICAL CA
42
Adenocarcinoma in situ of endocervical
type showing nuclear irregularity, size
variability, mitoses and apoptosis
Adenocarcinoma in situ. There is atypical
epithelium characterized by pseudostratifi
ed nuclei and hyperchromasia

43. COMPLICATIONS
 Pyometra – due to endocervical obstruction.
 Vesico-vaginal fistula - due to bladder invasion.
 Recto-vaginal fistula (rare) from rectal invasion.
 Ureteric obstruction with hydroureter,
hydropelvis, hydronephrosis and pyonephrosis.
 Uraemia
 Haemorrhage
 Cachexia
43

44. TREATMENT
 Depends on the stage on the disease
 Modalities include
 Surgery
 Radiotherapy
 Chemotherapy
 Combination of the above
 Radiotherapy can be used for all stages but
surgery is the treatment of choice for early
invasive cancer (stage I and IIA disease)
44

45. TREATMENT
 In more advanced cases, radiation combined
with chemotherapy is the current standard of
care 6
 In patients with disseminated disease,
chemotherapy or radiation provides symptom
palliation.
 bleeding, pelvic pain and urinary or partial large
bowel obstructions resulting from pelvic disease
45

46. TREATMENT
 Adjuvant chemoradiation is used in patients
discovered to have high-risk cervical cancer
after radical hysterectomy and in patients
with locally advanced cervical cancer (Peter’s
criteria)
 Pathologically involved lymph nodes
 Microscopic parametrial invasion
 Positive surgical margins.
46

47. TREATMENT SUMMARY
47

48. CLASSIFICATION OF
HYSTERECTOMY
48

49. COMPLICATIONS
49

50. SURVIVAL RATE
50

51. PREVENTION
 Comprehensive prevention involves the use
of diverse tools suitably applied to the
resources available –Global Guidance for cervical
cancer Prevention and Control (FIGO- 2009 and
2012)
 Primary prevention/Effective Advocacy
 Secondary prevention
 Tertiary prevention
 A functional National cancer registry
51

52. ADVOCACY: SOGON SUGGESTION FOR
NATIONAL CERVICAL SCREENING
PROGRAM
 All women aged 30-64 years should have
screening at least once in their life time
 Coverage should aim at 40% first year of
program, 60% coverage second year, 90% by the
fifth year, to make a sustainable impact on
cancer reduction and death
 Age at first test- 30 years or 2 years after the
first childbirth
 Screening interval 3-yearly
 High coverage is vital in the prevention strategy
and impacts on incidence reduction 52

53. 53
PRIMARY PREVENTION
Girls 9-13 years
• HPV vaccination
Girls and boys, as
appropriate
• Health information and
warnings about tobacco
use
• Sexuality education
tailored to age & culture
• Condom
promotion/provision for
those engaged in sexual
activity
• Male circumcision
SECONDARY PREVENTION
Women >30 years of age
Screening and treatment as
needed
• “Screen and treat” with low
cost technology VIA followed
by cryotherapy
• HPV testing for high risk
HPV types (e.g. types 16, 18
and others)
TERTIARY PREVENTION
All women as needed
Treatment of invasive
cancer at any age
• Ablative surgery
• Radiotherapy
• Chemotherapy
• Ensuring good quality
of life for the severely
affected e.g palliative
care, counselling to
cope with colostomy,
e.tc.
OVERVIEW OF PROGRAMMATIC
INTERVENTIONS for CANCER CONTROL

54. PREVENTION:VACCINATION
 Two vaccines- now available
 Bivalent Vaccine
 Quadrivalent vaccine
 Characteristics of these vaccines:
54

55. 55
Quadrivalent vaccine Bivalent Vaccine
Manufacture Merck (Gardasil ® also marketed
as Silgard ®)
GlaxoSmithKline
(CervarixTM)
VLPs of HPV
genotypes
6, 11,16, and 18 16 and 18
Substrate Yeast (S.cerevisiae) Baculovirus expression
system
Adjuvant Proprietary aluminium
hydroxyphosphate sulphate, 225
μg (Merck aluminium adjuvant)
Proprietary aluminium
hydroxide, 500μg , plus
50μg 3-deacylated
monophosphoryl lipid A
(GSK AS04 adjuvan)
Shedule used in trial-
three doses with
interval off:
Two months between dose 1 and
2; six month between dose 1 and 3
(0, 2, 6 schedule)
One month between dose 1
and 2; six months between
doses 1 and 3 (0, 1, 6
schedule)
Storage & Transport Requires cold chain system, stored
and transported at 2o C to 8o C
Should not be frozen
Requires cold chain system,
stored and transported at
2o C to 8o C
Should not be frozen
Approved licences as
of Feb 2009 and
WHO
prequalification
Licensed in 109 countries WHO
prequalified
Licensed in 92 countries
WHO prequalified

56. PREVENTION: CA REGISTRY
 HPV vaccination: vaccination coverage, by
year of age and by dose.
 Screening and treatment of precancers:
screening coverage, screening test positivity
rate, and treatment rate.
 Treatment of cancers: proportion of curable
cancer patients who get adequate treatment
and survival rates.
 Palliative care: opioid access for women with
advanced cervical cancer. 56

57. SUMMARY
 HPV is the major cause of ca cervix which is
established in the presence of other
favourable factors
 Pap smear among other tests are used for its
early detection.
 Presentation may be asymptomatic especially
in the early stages
 Treatment depends on the stage of the
diseases
 Survival can be very high when treated early57

58. CONCLUSION
Available evidences have shown that HPV plays a
vital role in the cause of cancer of the cervix and
recent researches have continued to make its
management possible. Therefore, personal lifestyle
modification, effective screening facilities coupled
with prompt and appropriate management with
favourable government policies will help to curb the
menace of the disease and thereby reduce its
morbidity and mortality
58

59. RESOURCES
1. Hoffman BL, Schorge JO, Bradshaw KD, Halvorson LM, Schaffer
JI, Corton MM. Williams gynecology. McGraw Hill Professional.
2016 Apr 22.
2. Kwawukume EY, Emuveyan EE. Comprehensive Obstetrics in
the Tropics 1st edition. Assante & Hittscher Printing Press Ltd.
2002
3. Ebughe GA, Ekanem IA, Omoronyia OE, Omotoso AJ, Ago BU,
Agan TU, Ugbem TI. Incidence of Cervical Cancer in Calabar,
Nigeria.
4. Campbell S, Monga A, editors. Gynaecology by ten teachers.
London: Arnold; 2000 Sep 20.
5. Kumar V, Abbas AK, Fausto NR, Aster JR. Cotran. Pathological
basis of diseases. 7th edition: Elsevier Singapore. 2006;289.
59

60. RESOURCES
6. Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology E-Book.
Elsevier Health Sciences. 2017 Mar 8.
7. Saxena R. Bedside Obstetrics & Gynecology. JP Medical Ltd;
2014 Mar 20.
8. Bruni L, Barrionuevo-Rosas L, Albero G, Serrano B, Mena M,
Gómez D, Muñoz J, Bosch FX, de Sanjosé S. ICO/IARC
Information Centre on HPV and Cancer (HPV Information
Centre). Human Papillomavirus and Related Diseases in
Nigeria. Summary Report 27 July 2017. [Accessed 20th April,
2018]
9. Etedafe PG. Cervical cancer: Advances in prevention.
Presentation for Part one update course in Obstetrics and
Gynaecology. 2014.
60

61. 61
THANK YOU
FOR LISTENING