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Ca cervix
JLENGWE
• anatomy of the cervix
• physiology of the cervix
• ca cervix
-definition
-epidemiology
-risk factor
-causes
-pathophysiology
-pathogenesis
-management
.investigation and staging
.treatment
-prognosis
-prevention
• The cervix is a cylinder-
shaped neck of tissue
that connects the vagina
and uterus.
• Located at the
lowermost portion of
the uterus, the cervix is
composed primarily of
fibromuscular tissue
anatomy
• 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. It is lined by stratified squamous non-
keratinized epithelium. The opening in the ectocervix, the
external os, marks the transition from the ectocervix to the
endocervical canal
• The endocervical canal (or endocervix) is the more proximal,
and ‘inner’ part of the cervix. It is lined by a mucus-secreting
simple columnar epithelium. The endocervical canal ends,
and the uterine cavity begins, at a narrowing called the
internal os
• the all entire cervix is about 2-5cm length when not
pregnant.
relations
• anteriorly: urinary bladder
• posteriorly: - pouch of
douglas and rectum
• superiorlly: uterus
• inferiorlly: vagina
• laterally: parametria
vascular supply
• arteries: via uterine arteries and vaginal arteries
• venous drainage: uterine venous plexus
• nerve supply: inferior nerve fibres of the uterovaginal plexus,The
afferent fibres mostly ascend through the inferior hypogastric plexus
to enter the spinal cord via T10-T12 and L1 nerve fibres
• lymphatic drainage: internal and external iliac nodes, sacral nodes
and superficial inguinal nodes
physiology
• The cervix performs two main functions:
• It facilitates the passage of sperm into the uterine cavity.
This is achieved via dilation of the external and internal os.
• Maintains sterility of the upper female reproductive tract.
The cervix, and all structures superior to it, are sterile. This
ultimately protects the uterine cavity and the upper genital
tract by preventing bacterial invasion. This environment is
maintained by the frequent shedding of the endometrium, thick
cervical mucus and a narrow external os
CA CERVIX
epidemiology
• Cervical cancer is the second most common cancer in women
worldwide
• Is the most common in Zambia
• Incidence 500,000 cases/year
• >270,000 deaths reported each year (WHO)
risk factors
• major risk factor is persistent HPV infection
• risk factors may reflect exposure to HPV
-Early onset of coitus
-Multiple sexual partners
-Sex with partner who has multiple sexual partners
-sex with uncircumcised men
• others includes
-Smoking
-Immunosuppression(HIV, prolonged steroids use)
-Low socio-economic status
-prolonged use of contraceptives
-multiparity
-diethylstilboestrol exposure in utero
causes
• HPV type 16 , 18, 31, 33 and 45 cause cancer
-hpv is sexually transmited
-its a small DNA virus
-more than 100 different types
-classified as low-risk or high-risk types, depending on their
ability to cause cancer.
• type 6 and 11 cause genital warts
pathophysiology
• The tubular cervix is composed of stromal tissue covered by
-squamous epithelium in the vagina (ectocervix)
-columnar epithelium within the cervical canal (endocervix).
• The endocervix contains many deep folds, called crypts, that are
lined by columnar epithelium.
• The meeting of the two types of epithelium is called the
squamocolumnar junction (SCJ) and this is usually on the
ectocervix.
• The position of the SCJ varies throughout life.
-In children it lies at the external cervical os,
-at puberty it extends outwards onto the ectocervix as the cervix
enlarges,
-and in adult life it returns to the external cervical os
• Metaplasia is the physiological transformation of columnar
epithelium to squamous epithelium.
• The so-called ‘transformation zone’ (TZ) is defined as the area
between the original SCJ and the current SCJ where the epithelium
changes from columnar to squamous epithelium over time.
• The TZ is the site where premalignancy and malignancy develop
pathogenesis
• high risk HPVs?
• HPV infects
• immature basal cells of the squamous epithelium
• immature metaplastic squamous cells
• HPV can not infect mature superficial squamous cells
• HPV infection results in production of viral proteins E6 and
E7
• these interfere with the activity of tumour suppressor
proteins that regulate cell growth and survival
• E7
• binds hypophosphorylated RB promoting its
degradation via proteasome pathway
• binds and inhibits p21 and p27 (CDKIs)
• results in enhanced cell cycle progression and impaired
ability to repair DNA damage
• E6
• binds p53-tumour suppressor protein promoting its
degradation
• up regulates the expression of telomerase=> cell
immortality
• net effect=> increased cellular proliferation
• normal-CIN 1- CIN 2- CIN 3
• SCC most common 80%
• adenocarcinoma 15%
• others (small cell carcinoma, adenosquamous) 5%
symptoms
Tend to appear only at advanced stage and include:
• Irregular, intermenstrual or postcoital bleeding and postmenopausal
bleeding
• dyspareunia
• Pelvic pain
• Vaginal discomfort or foul smelling discharge
• B symptoms (weight loss, fever and night sweats)
• loss of appetite, fatigue
clinical features of local spread
• renal failure(ureteric and urinary bladder obstruction)
• frequency and dysuria
• weight loss
• hematuria
• rarely jaundice or dyspnoea
• bone pain
• vesico-vaginal and recto-vaginal fistula
investigations
 history and,
 physical examination
-VE
-Rectal exam( for assessing parametrial invasion
 Baselines
-FBC and DC,LFTs,RFTs,PCR,HPV DNA TESTING
-urine cytology
 abdomen + pelvic u/s, CT scan or MRI of the abdomen and
pelvis
 Chest X-ray and pelvic X-rays for metastasis
 cystoscopy and cervical biopsy, and sigmoidoscopy
SCREENING METHOD
• Cancer screening is the systematic testing and or examination
of a population in order to detect a cancer before it causes
symptoms.
• The utility of a screening test depends on the ability to detect a
true positive (sensitivity) and the ability to reject a true
negative (specificity)
FACTORS TO CONSIDER
• Is the disease curable if diagnosed early?
• What is the sensitivity of the test used?
• Is the disease common?
• How frequently should the test be done?
• What population should be tested?
• What are the disadvantages of screening?
'WHO' CONSIDERATION FOR SUCCESSFUL
SCREENING
1. The population to screen should be agreed
2. The test should be acceptable
3. Screening is for a condition of importance
4. Latent period allows for intervention
5. The disease natural history is well understood
6. Diagnostic facilities are available
7. Appropriate test is available
8. Effective early treatment is available
9. The programme is cost effective
10.Screening should be continuous
PURPOSE OF SCREENING
• For screening to be beneficial, the earlier detection and
treatment must impact on mortality, increasing lifespan.
SCREENING METHODS
AVAILABLE FOR Ca CERVIX
1. PAPS SMEAR
2. VIA
3. VILI
4. COLPOSCOPY
5. HPV DNA TESTING
1. PAPS SMEAR
• PAPs SMEAR
-goldstard
-Dr. George Papanicolaou
-French Anatomist
paps smear con't....
• Screening test used to detect potentially pre-cancerous and cancerous
processes in the endocervical canal (transformation zone) of the female
reproductive system.
• The Pap smear test involves collecting, staining and examining a sample of
cells from the cervix (focusing on the transformation zone)
• Abnormal cells can be detected at an early stage
pap smear con't...
• Effective follow-up interventions can then prevent the
development of cervical cancer
• Pap test sensitivity for detecting cervical intraepithelial
neoplasia (CIN) is relatively low (50%)
• Specificity is up to 92-98%
• Therefore; repeat testing with other highly sensitive methods is
recommended
Types of paps smear
1. Conventional
• Samples are smeared directly onto a microscope slide after collection and a
fixative is applied
2. Liquid based cytology
• Sample is put in a bottle of preservative for transport to the laboratory,
where it is then smeared on the slide
• Increases accuracy of screening
• Preservative liquid used can also be tested for HPV DNA
paps smear results
Five Possible outcomes
1. Normal
2. Atypical Squamous Cells of Undetermined significance (ASCUS)
3. Atypical Granular Cells of Undetermined significance (AGCUS)
4. Low grade intraepithelial lesion = CIN I
5. High grade intraepithelial lesion = CIN II and CIN III
6. When abnormal cells are detected on the Pap Test,
7. Diagnostic testing in the form of colposcopy is often indicated
2. visual inspection with acetic
acid(VIA)
• Used in low-resource settings
• Cheaper and simpler than Pap smear
• Identifies cervix lesion without the use of cytology
• Cervix is cleaned with dry swab
• It is then swabbed with 3-5% acetic acid
• Wait for 1 minute
• 50% sensitivity, has lower specificity than Pap smear
• Screening interval of 3 years if negative results
• Due to differences in pre-cancerous cell opacity and structure,
abnormal cells appear white
VIA
ADVANTAGES
• Easy to use (simple)
• Low cost
• Immediate results
• High coverage
• Does not need expertise
DISADVANTAGES
• Low specificity
3.VISUAL INSPECTION WITH
LUGOL’S IODINE (VILI)
• Based on clinical examination with speculum, potassium iodine applied to
the cervix 1 minute, and visual determination of disease by trained health
care worker.
• VILI findings depend on interaction between iodine & glycogen
• Glycogen abundant in normal, mature squamous epithelium
-Little or no glycogen in abnormal epithelium
• A dark brown cervix equates a negative test
• Colourless, pale or mustard yellow cervix equates a positive test
4. COLPOSCOPY
• Looks at cervix using binocular microscope for magnification
• Indicated if Pap smear shows abnormal results
• Patient lies in dorsal lithotomy position
• Acetic acid or Lugol’s iodine is used to highlight abnormal areas
• Enable suspected tissue to be biopsied and/or removed
• Colposcopy helps make the distinction between a mare lesion
and an invasive state
5. HPV DNA TESTING
• Detects lesions which cause cervical cancer earlier in women
between 30 and 65 years
• Only detects HPV infection present at the time of the test
• Does not detect abnormal cells in the cervix
• Testing positive still requires other tests e.g. Pap smear
• A positive HPV DNA test indicates the presence of a high-risk
type of HPV, but the test does not specify which type is present
BARRIER TO SCREENING
• Lack of cervical cancer knowledge/understanding
• Limited understanding of female body and associated diseases
• Limited access to services
• Shame, embarrassment and fear of a vaginal examination
• Fear of death from cancer
• Partner/family
• Lack of trust in health care system
• Lack of support from community and family
• ‘Preventive care’ concept is unknown
HOW TO IMPROVE OUR SCREENING
PROGRAM
• Health promotion through education
• Targeting those never screened
• Better training and health education of practitioners
• Sensitivity to social and cultural factors
staging (FIGO)
Treatment approaches
STAGES TREATMENT OPTION
1A1
-simple hysterectomy with/without oophorectomy
-knife cone biopsy for those who wish to retain fertility
-intracavitary brachytherapy for those that are unfit for surgery
1A2
-radical hysterectomy
-radical trachelectomy for those who wish to retain fertility
-radical radiotherapy for those that are medically unfit for surgery
1B1
-radical hysterectomy
-radical radiotherapy
1B to 4A -concurrent cisplatin based chemotherapy and radiotherapy
4B -palliative treatment aimed to improving their quality of life
Chemoradiation toxicities
 acute effects
-tiredness
-anaemia
-myelosuppression/ neutropenic sepsis
-diarrhoea
-proctitis
-skin reaction
-nausea
-peripheral neuropathy
-renal impairment
-hypocalcemia and hypomagnesaemia
chemoradiation toxicities
 late effect
-bowel strictures and bowel perforations
-rectal bleeding
-reduced bladder capacity, detrussor instability
-vaginal shortening and narrowing
-chemoradiation induced menopause
-infertility
prognosis
• adverse tumor related prognostic factors in cervical cancer
includes-:
-increase tumor bulk
-presence of lymph node metastasis
-lymphovascular space invasion
-increased cancer stage
adenocarcinoma
prognosis con't..
• patient related factors
-anaemia
-poor performance status
• adverse treatment related factors
-long radiation therapy
-no intracavitary brachytherapy rediation
-positive surgical resection margin
prevention
prevention.....prevention............
prevention................prevention
levels of disease prevention
• Primary prevention: prevents diseases from occurring; reduces
incidence example vaccination (HPV 16 and 18)
-Gardasil, Cervarix and Gardasil 9
• Secondary prevention: early disease detection, delays onset and
duration of disease; to improve survival e.g. cervical cancer
screening
-Not necessarily designed to prevent occurrence of disease but rather
decrease morbidity and mortality
• Tertiary prevention: slows disease progression; reduces disease
sequelae;
-To improve survival or quality of life
TWALUMBA

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Cervical cancer ppt

  • 2. • anatomy of the cervix • physiology of the cervix • ca cervix -definition -epidemiology -risk factor -causes -pathophysiology -pathogenesis -management .investigation and staging .treatment -prognosis -prevention
  • 3. • The cervix is a cylinder- shaped neck of tissue that connects the vagina and uterus. • Located at the lowermost portion of the uterus, the cervix is composed primarily of fibromuscular tissue anatomy
  • 4. • 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. It is lined by stratified squamous non- keratinized epithelium. The opening in the ectocervix, the external os, marks the transition from the ectocervix to the endocervical canal
  • 5. • The endocervical canal (or endocervix) is the more proximal, and ‘inner’ part of the cervix. It is lined by a mucus-secreting simple columnar epithelium. The endocervical canal ends, and the uterine cavity begins, at a narrowing called the internal os • the all entire cervix is about 2-5cm length when not pregnant.
  • 6.
  • 7. relations • anteriorly: urinary bladder • posteriorly: - pouch of douglas and rectum • superiorlly: uterus • inferiorlly: vagina • laterally: parametria
  • 8. vascular supply • arteries: via uterine arteries and vaginal arteries • venous drainage: uterine venous plexus • nerve supply: inferior nerve fibres of the uterovaginal plexus,The afferent fibres mostly ascend through the inferior hypogastric plexus to enter the spinal cord via T10-T12 and L1 nerve fibres • lymphatic drainage: internal and external iliac nodes, sacral nodes and superficial inguinal nodes
  • 9.
  • 10. physiology • The cervix performs two main functions: • It facilitates the passage of sperm into the uterine cavity. This is achieved via dilation of the external and internal os. • Maintains sterility of the upper female reproductive tract. The cervix, and all structures superior to it, are sterile. This ultimately protects the uterine cavity and the upper genital tract by preventing bacterial invasion. This environment is maintained by the frequent shedding of the endometrium, thick cervical mucus and a narrow external os
  • 11.
  • 13. epidemiology • Cervical cancer is the second most common cancer in women worldwide • Is the most common in Zambia • Incidence 500,000 cases/year • >270,000 deaths reported each year (WHO)
  • 14. risk factors • major risk factor is persistent HPV infection • risk factors may reflect exposure to HPV -Early onset of coitus -Multiple sexual partners -Sex with partner who has multiple sexual partners -sex with uncircumcised men • others includes -Smoking -Immunosuppression(HIV, prolonged steroids use) -Low socio-economic status -prolonged use of contraceptives -multiparity -diethylstilboestrol exposure in utero
  • 15. causes • HPV type 16 , 18, 31, 33 and 45 cause cancer -hpv is sexually transmited -its a small DNA virus -more than 100 different types -classified as low-risk or high-risk types, depending on their ability to cause cancer. • type 6 and 11 cause genital warts
  • 16. pathophysiology • The tubular cervix is composed of stromal tissue covered by -squamous epithelium in the vagina (ectocervix) -columnar epithelium within the cervical canal (endocervix). • The endocervix contains many deep folds, called crypts, that are lined by columnar epithelium. • The meeting of the two types of epithelium is called the squamocolumnar junction (SCJ) and this is usually on the ectocervix.
  • 17.
  • 18. • The position of the SCJ varies throughout life. -In children it lies at the external cervical os, -at puberty it extends outwards onto the ectocervix as the cervix enlarges, -and in adult life it returns to the external cervical os • Metaplasia is the physiological transformation of columnar epithelium to squamous epithelium. • The so-called ‘transformation zone’ (TZ) is defined as the area between the original SCJ and the current SCJ where the epithelium changes from columnar to squamous epithelium over time. • The TZ is the site where premalignancy and malignancy develop
  • 19.
  • 20. pathogenesis • high risk HPVs? • HPV infects • immature basal cells of the squamous epithelium • immature metaplastic squamous cells • HPV can not infect mature superficial squamous cells
  • 21. • HPV infection results in production of viral proteins E6 and E7 • these interfere with the activity of tumour suppressor proteins that regulate cell growth and survival
  • 22.
  • 23. • E7 • binds hypophosphorylated RB promoting its degradation via proteasome pathway • binds and inhibits p21 and p27 (CDKIs) • results in enhanced cell cycle progression and impaired ability to repair DNA damage
  • 24. • E6 • binds p53-tumour suppressor protein promoting its degradation • up regulates the expression of telomerase=> cell immortality • net effect=> increased cellular proliferation
  • 25. • normal-CIN 1- CIN 2- CIN 3 • SCC most common 80% • adenocarcinoma 15% • others (small cell carcinoma, adenosquamous) 5%
  • 26. symptoms Tend to appear only at advanced stage and include: • Irregular, intermenstrual or postcoital bleeding and postmenopausal bleeding • dyspareunia • Pelvic pain • Vaginal discomfort or foul smelling discharge • B symptoms (weight loss, fever and night sweats) • loss of appetite, fatigue
  • 27. clinical features of local spread • renal failure(ureteric and urinary bladder obstruction) • frequency and dysuria • weight loss • hematuria • rarely jaundice or dyspnoea • bone pain • vesico-vaginal and recto-vaginal fistula
  • 28. investigations  history and,  physical examination -VE -Rectal exam( for assessing parametrial invasion  Baselines -FBC and DC,LFTs,RFTs,PCR,HPV DNA TESTING -urine cytology  abdomen + pelvic u/s, CT scan or MRI of the abdomen and pelvis  Chest X-ray and pelvic X-rays for metastasis  cystoscopy and cervical biopsy, and sigmoidoscopy
  • 29. SCREENING METHOD • Cancer screening is the systematic testing and or examination of a population in order to detect a cancer before it causes symptoms. • The utility of a screening test depends on the ability to detect a true positive (sensitivity) and the ability to reject a true negative (specificity)
  • 30. FACTORS TO CONSIDER • Is the disease curable if diagnosed early? • What is the sensitivity of the test used? • Is the disease common? • How frequently should the test be done? • What population should be tested? • What are the disadvantages of screening?
  • 31. 'WHO' CONSIDERATION FOR SUCCESSFUL SCREENING 1. The population to screen should be agreed 2. The test should be acceptable 3. Screening is for a condition of importance 4. Latent period allows for intervention 5. The disease natural history is well understood 6. Diagnostic facilities are available 7. Appropriate test is available 8. Effective early treatment is available 9. The programme is cost effective 10.Screening should be continuous
  • 32. PURPOSE OF SCREENING • For screening to be beneficial, the earlier detection and treatment must impact on mortality, increasing lifespan.
  • 34. 1. PAPS SMEAR 2. VIA 3. VILI 4. COLPOSCOPY 5. HPV DNA TESTING
  • 35. 1. PAPS SMEAR • PAPs SMEAR -goldstard -Dr. George Papanicolaou -French Anatomist
  • 36. paps smear con't.... • Screening test used to detect potentially pre-cancerous and cancerous processes in the endocervical canal (transformation zone) of the female reproductive system. • The Pap smear test involves collecting, staining and examining a sample of cells from the cervix (focusing on the transformation zone) • Abnormal cells can be detected at an early stage
  • 37. pap smear con't... • Effective follow-up interventions can then prevent the development of cervical cancer • Pap test sensitivity for detecting cervical intraepithelial neoplasia (CIN) is relatively low (50%) • Specificity is up to 92-98% • Therefore; repeat testing with other highly sensitive methods is recommended
  • 38. Types of paps smear 1. Conventional • Samples are smeared directly onto a microscope slide after collection and a fixative is applied 2. Liquid based cytology • Sample is put in a bottle of preservative for transport to the laboratory, where it is then smeared on the slide • Increases accuracy of screening • Preservative liquid used can also be tested for HPV DNA
  • 39.
  • 40. paps smear results Five Possible outcomes 1. Normal 2. Atypical Squamous Cells of Undetermined significance (ASCUS) 3. Atypical Granular Cells of Undetermined significance (AGCUS) 4. Low grade intraepithelial lesion = CIN I 5. High grade intraepithelial lesion = CIN II and CIN III 6. When abnormal cells are detected on the Pap Test, 7. Diagnostic testing in the form of colposcopy is often indicated
  • 41. 2. visual inspection with acetic acid(VIA) • Used in low-resource settings • Cheaper and simpler than Pap smear • Identifies cervix lesion without the use of cytology • Cervix is cleaned with dry swab • It is then swabbed with 3-5% acetic acid
  • 42. • Wait for 1 minute • 50% sensitivity, has lower specificity than Pap smear • Screening interval of 3 years if negative results • Due to differences in pre-cancerous cell opacity and structure, abnormal cells appear white
  • 43.
  • 44. VIA ADVANTAGES • Easy to use (simple) • Low cost • Immediate results • High coverage • Does not need expertise DISADVANTAGES • Low specificity
  • 45. 3.VISUAL INSPECTION WITH LUGOL’S IODINE (VILI) • Based on clinical examination with speculum, potassium iodine applied to the cervix 1 minute, and visual determination of disease by trained health care worker. • VILI findings depend on interaction between iodine & glycogen • Glycogen abundant in normal, mature squamous epithelium -Little or no glycogen in abnormal epithelium • A dark brown cervix equates a negative test • Colourless, pale or mustard yellow cervix equates a positive test
  • 46.
  • 47.
  • 48. 4. COLPOSCOPY • Looks at cervix using binocular microscope for magnification • Indicated if Pap smear shows abnormal results • Patient lies in dorsal lithotomy position • Acetic acid or Lugol’s iodine is used to highlight abnormal areas • Enable suspected tissue to be biopsied and/or removed • Colposcopy helps make the distinction between a mare lesion and an invasive state
  • 49.
  • 50.
  • 51. 5. HPV DNA TESTING • Detects lesions which cause cervical cancer earlier in women between 30 and 65 years • Only detects HPV infection present at the time of the test • Does not detect abnormal cells in the cervix • Testing positive still requires other tests e.g. Pap smear • A positive HPV DNA test indicates the presence of a high-risk type of HPV, but the test does not specify which type is present
  • 52. BARRIER TO SCREENING • Lack of cervical cancer knowledge/understanding • Limited understanding of female body and associated diseases • Limited access to services • Shame, embarrassment and fear of a vaginal examination • Fear of death from cancer • Partner/family • Lack of trust in health care system • Lack of support from community and family • ‘Preventive care’ concept is unknown
  • 53. HOW TO IMPROVE OUR SCREENING PROGRAM • Health promotion through education • Targeting those never screened • Better training and health education of practitioners • Sensitivity to social and cultural factors
  • 55. Treatment approaches STAGES TREATMENT OPTION 1A1 -simple hysterectomy with/without oophorectomy -knife cone biopsy for those who wish to retain fertility -intracavitary brachytherapy for those that are unfit for surgery 1A2 -radical hysterectomy -radical trachelectomy for those who wish to retain fertility -radical radiotherapy for those that are medically unfit for surgery 1B1 -radical hysterectomy -radical radiotherapy 1B to 4A -concurrent cisplatin based chemotherapy and radiotherapy 4B -palliative treatment aimed to improving their quality of life
  • 56. Chemoradiation toxicities  acute effects -tiredness -anaemia -myelosuppression/ neutropenic sepsis -diarrhoea -proctitis -skin reaction -nausea -peripheral neuropathy -renal impairment -hypocalcemia and hypomagnesaemia
  • 57. chemoradiation toxicities  late effect -bowel strictures and bowel perforations -rectal bleeding -reduced bladder capacity, detrussor instability -vaginal shortening and narrowing -chemoradiation induced menopause -infertility
  • 58. prognosis • adverse tumor related prognostic factors in cervical cancer includes-: -increase tumor bulk -presence of lymph node metastasis -lymphovascular space invasion -increased cancer stage adenocarcinoma
  • 59. prognosis con't.. • patient related factors -anaemia -poor performance status • adverse treatment related factors -long radiation therapy -no intracavitary brachytherapy rediation -positive surgical resection margin
  • 61. levels of disease prevention • Primary prevention: prevents diseases from occurring; reduces incidence example vaccination (HPV 16 and 18) -Gardasil, Cervarix and Gardasil 9 • Secondary prevention: early disease detection, delays onset and duration of disease; to improve survival e.g. cervical cancer screening -Not necessarily designed to prevent occurrence of disease but rather decrease morbidity and mortality • Tertiary prevention: slows disease progression; reduces disease sequelae; -To improve survival or quality of life