Cervical cancer

1. Current update on the
prevention and management of
cervical cancer
Dr Muhammed Khadijat Ayo
Department of histopathology
Dalhatu Araf Specialist Hospital

2. Outline of presentation
• Introduction
• Risk factors
• Etiology
• Pathophysiology
• Prevention
• Management of precancerous Lesion
• Staging of cervical cancer
• Management
• Conclusion

3. Introduction
• Cervical cancer is the fourth most common malignancy in women
worldwide.
• Cervical cancer is a public health problem all over the world, even
though it is preventable.
• Its incidence, morbidity and mortality has significantly reduced in
countries with organized, population-based routine prevention (both
primary and secondary) programs.
• Most LMIC, including Nigeria, have not achieved this.
• The WHO has adopted the 90:70:90 strategy to eliminate cervical
cancer as a public health problem by 2030.

4. Risk Factors
• Multiple sexual
• Early coitarche (pre-menarcheal: susceptible cervix)
• Early marriage
• Early age at first pregnancy
• Early age at first child birth
• High parity
•Low socio-economic status
• Cigarette smoking
• Immunosuppression

5. Aetiology
► Cervical cancer is caused by high risk human papillomavirus (HrHPV),
with 70% of all invasive cervical cancer related to HPV16/18.
► The pathogenesis involves sexually transmitted infection with
HrHPV):
► innate immune clearance (with regression to normal):
► or persistence (with regression to normal or progression):
► LSILs (with regression to normal):
► HSILs (with regression to normal):
► invasive disease.

6. Aetiology
•Oncogenic (High risk) types of the Human Papilloma Virus are
(16, 18, 31, 33, 35, 39, 45, 51, 52, and 58).
•non-oncogenic or low-risk types (6, 11, 40, 42, 43, 44, and 54)
that are associated with genital warts(Muñoz, 2003).
•HPV 16 is the most oncogenic, accounting for almost half of all
cervical cancers

7. Aetiology
• HPV 16 and 18 together account for approximately 70% of cervical
cancers
• HPV 6 and 11 are the most common strains associated with genital
warts and are responsible for approximately 90% of these lesions.
• On average, only 5% of HPV infections will result in the
development of CIN grade 2 or 3 lesions (the recognized cervical
cancer precursor) within 3 years of infection. Only 20% of CIN 3
lesions progress to invasive cervical cancer within 5 years, and only
40% of CIN 3 lesions progress to invasive cervical cancer with 30
years.

8. Pathophysiology

9. Pathophysiology

10. Pathophysiology
• The viral genome encodes 6 early open reading frame proteins (ie,
E1, E2, E3, E4, E6, and E7), which function as regulatory proteins,
and 2 late open reading frame proteins (ie, L1 and L2), which make
up the viral capsid.
• E7 binds and inactivates the Rb protein while E6 binds p53 and
directs its degradation, and the functional loss of the P53 and RB
genes leads to resistance to apoptosis, causing uncensored cell
growth after DNA damage.
• This ultimately results in progression to malignancy.

11. Pathophysiology

13. Cervical intraepithelial neoplasia
It represents a spectrum of intraepithelial changes (dysplasia with
indistinct boundary that brings with atypical mild atypia and
progresses through stages of more marked intraepithelial
abnormalities to carcinoma in situ.

14. Grading of Precancerous Lesion (cervical intraepithelial
neoplasia CIN)
• CIN I low grade intraepithelial lesions in which dysplastic cell
occupy the lower third of epithelium epithelium
• High grade squamous intraepithelial lesion (HGISL) it
encompasses CIN 2 and 3 in which dysplastic cells occupy up to
the middle third and upper third of the epithelium respectively
• Atypical squamous cells of undetermined significance ASCUS
• Atypical squamous cell cannot exclude HGSIL

15. ► Primary
► Behavioural modifications
► HPV Vaccinations
► Secondary (screening)
► Pap Smear
►Self sampling (
► HPV DNA Testing
►Self sampling
► Visual Inspection
► AVA
► Guidelines
Prevention

16. ► Screening is a secondary preventive measure to identify early exposure
(infection) with HrHPV, premalignant lesions or curable early disease.
► It implies exposure already
► 3 main methods
► When to start/stop
► Screening intervals
► Different co-testing combinations
► Different guidelines
Best Approach: the most effective for sustainable population screening
in a particular setting.
Screening Approaches

17. ► Pap smear uses cytology to identify premalignant lesions of the cervix.
► HPV test looks for the human papillomavirus DNA in cervic, a virus that
can cause cervical cancer.
► HPV/Pap cotest, an HPV test and a Pap test are done together.
► Self-sampling
► Visual inspection
► (Colposcopy and biopsy)
Screening Approaches

18. Screening Approaches

19. Screening Approaches -Sogon

20. Screening Approaches -NSPPCCCN

21. 5.3.1 American Cancer Society
► ACS recommends cervical cancer screening with an HPV test alone every 5 years for everyone with a
cervix from age 25 until age 65.
► If HPV testing alone is not available, people can get screened with an HPV/Pap cotest every 5 years
or a Pap test every 3 years.
Screening Approaches American Cancer society

22. Why does the new guideline recommend an HPV test over a Pap test or HPV/Pap cotest?
► All three tests can find cervical cancer precursors before they become cancer. But studies have
shown that HPV tests are more accurate and more reliable than Pap tests. Also, you can rule out
disease really well with HPV tests so they don’t have to be repeated as frequently.
► Although the Pap test has led to huge drops in rates of cervical cancer and death from the
disease, it has some limitations. Pap tests have lower sensitivity compared with HPV tests, so
they may miss some precancers and have to be repeated frequently. They also detect a range of
abnormal cell changes, including some minor changes that are completely unrelated to HPV. So,
many people who get an abnormal Pap test result actually have a very low chance of developing
cervical cancer.
► HPV/Pap cotesting is only slightly more sensitive than HPV testing, but it is less efficient because
it requires two tests. And it detects a lot of minor changes that have a very low risk of turning
into cancer. For an entire population, that’s a lot of additional effort and cost.
► Screening with an HPV test alone was not recommended by ACS in 2012 because that approach
wasn’t yet approved by FDA. The 2018 USPSTF guideline included HPV testing alone, cotesting,
and Pap testing as equal options. The difference in the new ACS guidelines is that
they elevate HPV testing alone over the other two tests.
Screening Approaches American Cancer society

23. Why does the new guideline recommend screening starting at age 25, instead of age 21?
► Using information from new studies, ACS concluded that the benefits of cervical cancer screening do not
outweigh the harms for people aged 21 to 24 years old.
► This is an important change that is related to HPV vaccines. The first cohort of women who received the
HPV vaccine when they were younger are now in their 20s and are eligible for cervical cancer screening.
HPV vaccines are very good at preventing HPV infections, particularly infection with HPV types 16 and 18,
the types that cause most cervical cancers. So, the vaccines have led to a drop in HPV infections and
cervical precancer in this age group.
► Also, in young women, most HPV infections go away on their own. Screening people in this age group often
leads to unnecessary treatment, which can have side effects. That’s why ACS recommends starting
screening at age 25.
Screening Approaches American Cancer society

24. Have the recommendations for those who are 65 years old or older changed?
► No, the recommendations for this age group are the same as before. If you’ve had a series of normal
screening test results over a long period of time, then you can stop screening at age 65. If, in the past, you
had an abnormal result or anything suspicious on a screening test, or had treatment for cervical cancer or
precancer, then you should continue to be screened.
► The recommended age limit for cervical cancer screening has been consistent across different guidelines
over the years. But there are current efforts to study the age limit more because it’s an area where we
have less data. There is more interest now in looking at people who had an abnormal screening test result
at an older age to see if they require more years of screening or more frequent screening.
Screening Approaches American Cancer society

25. these screening tests save lives, isn’t it better for people to get tested more often and with more tests?
► No. As with many tests, there is the potential to do more harm than good if they are applied too
frequently. There are a few risks that come with cervical cancer screening tests.
► So, while testing more often or with more tests may seem like a good idea, it can actually lead to more
harms. ACS carefully evaluated the potential benefits and harms of each screening test for each age group
to come up with their updated recommendations.
Do people who got the HPV vaccine still need to get cervical cancer screening?
► Yes, the new guideline recommends screening for those who have had the HPV vaccine. It does not
recommend making a screening decision based on whether an individual has had the vaccine.
Screening Approaches American Cancer society

26. What happens after someone gets an abnormal cervical screening test result?
► If something abnormal or suspicious was found, also called a positive test result, you will typically get a
second test. The standard approach is to do a Pap test, but there is also a new FDA-approved test, called
dual stain. The dual stain test uses two biomarkers that can give a more accurate sign that precancer is
present.
► The results of the second test will help decide if you need a colposcopy—a procedure to look at the cervix
with a magnifying lens and take samples from spots on the cervix that look abnormal.
Screening Approaches American Cancer society

27. Screening Approaches American Cancer society

28. Screening Approaches WHO

29. Screening Approaches New WHO

30. New Researches
► Use of biomarkers in screening
► Exploring the omics in screening
► Scientifically determining what works for Nigeria.

31. Management of cervical intraepithelial lesions
A. Local ablative therapy
Cryotherapy
CO2 laser therapy
Electrocautery
cold coagulation
A. Excisional therapy
conization (cold knife or with laser)
Loop electrosurgical excision procedure
Simple extrafascial hysterectomy

32. Staging of cervical cancer(FIGO 2018)
• STAGE1
• IA: Invasive carcinoma that can be diagnosed only by microscopy with
measured deepest invasion <5.0 mm (involvement of
vascular/lymphatic spaces does not change the staging)
• IA1: Measured stromal invasion <3.0 mm
• IA2: Measured stromal invasion ≥3.0 mm and <5.0 mm
• IB: Invasive carcinoma with measured deepest invasion ≥5.0 mm,
limited to the cervix uteri
• IB1: Invasive carcinoma ≥5.0 mm depth of invasion and <2.0 cm in
greatest dimension
• IB2: Invasive carcinoma ≥2.0 cm and <4.0 cm in greatest dimension
• IB3: Invasive carcinoma ≥4.0 cm in greatest dimension

33. Staging of cervical cancer(FIGO 2018)
• STAGE 2
• IIA: Without parametrial invasion
• IIA1: Invasive carcinoma <4.0 cm in greatest dimension
• IIA2: Invasive carcinoma ≥4.0 cm in greatest dimension
• IIB: With parametrial invasion

34. Staging of cervical cancer(FIGO 2018)
• STAGE 3
• IIIA: Carcinoma involves the lower third of the vagina, with no
extension to the pelvic wall.
• IIIB: Extension to the pelvic wall and/or hydronephrosis or
non‐functioning kidney.
• IIIC: Involvement of pelvic and/or para aortic lymph nodes,
irrespective of tumor size and extent (with r and p notations.)
• IIIC1: Pelvic lymph node metastasis only
• IIIC2: Para‐aortic lymph node metastasis
• STAGE 4
• IVA: Spread to adjacent organs
• IVB: Spread to distant organs

35. Management
• Stage 0: Carcinoma in situ (stage 0) is treated with local ablative or
excisional measures such as
-cryosurgery
-laser ablation
-loop excision

36. Management
Stage IA1 cancer
• Total hysterectomy
• radical hysterectomy
• conization.
• Lymph node dissection is not required if the depth of invasion is
less than 3 mm and no lymphovascular invasion is noted.

37. • Selected patients with stage IA1 disease but no lymphovascular
space invasion who desire to maintain fertility may undergo
therapeutic conization with close follow-up.
ie. including cytology, colposcopy, and endocervical curettage.
• Radiation for patients with comorbid medical conditions who are
not surgical candidates.
• According to National Comprehensive Cancer Network (NCCN)
guidelines, pelvic radiation therapy is currently a category 1
recommendation for women with stage IA disease and negative
lymph nodes after surgery who have high-risk factors (eg, a large
primary tumor, deep stromal invasion, or lymphovascular space
invasion)

38. Management
•Stage IA2, IB, or IIA:
•radical vaginal trachelectomy with pelvic lymph node
dissection is appropriate for fertility preservation in
women with stage IA2 to IB cervical cancer with diameter
<2 cm and invasion <10 mm
•Combined external beam radiation with brachytherapy for
stage IB or IIA disease
•Radical hysterectomy with bilateral pelvic
lymphadenectomy for stage IB or IIA disease

39. Management

40. Management
• Other methods that help to preserve fertility:
• Cryopreservation of unfertilized oocytes as an option for patients
who do not have a male partner, do not wish to use donor sperm,
or have religious or ethical objections to embryo freezing
• Ovarian transposition (oophoropexy) is an option when pelvic
radiation therapy is performed; however, because of radiation
scatter, ovaries are not always protected, and patients should be
aware that this technique is not always successful
• Pelvic shielding during radiation

41. Management

43. Management
• Stage IIB, III, or IVA: Cisplatin-based chemotherapy with radiation
is the standard of care
• Stage IVB and recurrent cancer: Individualized therapy is used on
a palliative basis; radiation therapy is used alone for control of
bleeding and pain; systemic chemotherapy is used for
disseminated disease

44. Management
• Incidence of cervical cancer in pregnancy is 1 to 10 in 10,000
pregnancies
• Management is by a multidisciplinary team
• In the first trimester, there is no need for continuation of the
pregnancy
-EOU and surgery or chemoradiation
-Surgery involves a radical hysterectomy with ovarian
preservation
and pelvic lymphadenectomy
-Chemoradiation

45. Management
• In second trimester
-Unwanted pregnancy-chemoradiation
-Wanted pregnancy-Delay of 6 to 8 weeks up to fetal maturity
Chemotherapy may be considered until maturity
Caesarean section and staging laparotomy
Delivery followed by chemoradiation

46. Management
• In the third trimester
- Delay until maturity
- Chemotherapy may be given during waiting period
- Caesarean section and staging laparotomy
- Radiation therapy two weeks postpartum

47. Management
• Nerve sparing surgeries for cervical cancer
• Credited to Okabayashi
• Spares pelvic autonomic nerves
• Leads to a reduction of sexual and bladder dysfunction following
traditional radical hysterectomy

48. Management
• Recurrent cancer of the cervix
• Treatment based on
-performance status of the patient
-the site of recurrence and/or metastases
-the extent of metastatic disease, and prior treatment.

49. Management
• For local recurrence following radiotherapy-pelvic exenteration
• The 5-year survival rate for patients who undergo total pelvic
exenteration ranges from 30%-60%
• The prognosis is better for patients with a disease-free interval
greater than 6 months, recurrence <3 cm in diameter, and no side
wall fixation
• Local Recurrence of Cervical Cancer Following Radical Surgery-
radical radiation or pelvic exenteration

50. Management
• For metastatic tumour
-Chemoradioation
-Palliative care

51. Management

52. Prevention
Primary prevention
• Sexuality education tailored to age & culture
• Health information and warnings about tobacco use
• Education of girls
• ABC of STD prevention
• Male circumcision
• HPV Vaccination

53. Prevention
• Bivalent vaccine-Cervarix
• Effective against HPV 16 and 18
• IM Injection 0.5 mls at 0,1 and 6 months
• 70% Effective against cervical cancer

54. Prevention
• Quadrivalent Vaccine -Gardasil
• HPV types 6, 11, 16, and 18)
• HPV vaccine targets the HPV strains responsible for approximately
70% of cervical cancers and 90% of genital warts.
• Administered intramuscularly at 0, 1 and 6 months
• phylogenetically related to the vaccine HPV types (eg, 45 for 18,
31 and 33 for 16

55. Prevention
• Gardasil-9
• Recombinant vaccine that targets 9 HPV types (6, 11, 16, 18, 31,
33, 45, 52, and 58).
• Administered at 0,2 and 6 months

56. Prevention
• Protects against 90% of cervical cancer
• Since October 2016, CDC Recommendation-Give 2 doses of
Vaccines for ages 9-14 years 6 months apart.
• Give 3 doses from 15 years to 26 years.

57. Prevention
• Secondary prevention
• Screen and treat” with low cost technology VIA followed by
cryotherapy
• VILI
• HPV testing for high risk HPV types (e.g. types 16, 18 and others)
• PAP Smears

58. Prevention
• Current screening recommendations for specific age groups, based
on guidelines from the American Cancer Society (ACS), the
American Society for Colposcopy and Cervical Pathology (ASCCP),
the American Society for Clinical Pathology (ASCP), the US
Preventive Services Task Force (USPSTF), and the American
College of Obstetricians and Gynecologists (ACOG), are as follows

59. Prevention
• < 21 years: No screening recommended
• 21-29 years: Cytology (Pap smear) alone every 3 years
• 30-65 years: Human papillomavirus (HPV) and cytology cotesting
every 5 years (preferred) or cytology alone every 3 years
(acceptable)
• >65 years: No screening recommended if adequate prior screening
has been negative and high risk is not present

60. Prevention
• Tertiary prevention
• Treatment of invasive cancer at any age
• Surgery, Radiotherapy, Chemotherapy

61. Conclusion
• Cervical cancer is an important cause of morbidity and mortality
in women
• The way to reduce the menace of cervical cancer will be through a
rigid population based screening programme that is efficient.

63. References
• Muñoz N, Bosch FX, de Sanjosé S, et al. Epidemiologic
classification of human papillomavirus types associated with
cervical cancer. N Engl J Med. 2003;348:518–527
• https://emedicine.medscape.com/article/253513-overview#a3
• Guideline] National Comprehensive Cancer Network. NCCN
Clinical Practice Guidelines in Oncology: Cervical Cancer Version
1.2016. Available at
http://www.nccn.org/professionals/physician_gls/PDF/cervical.p
df. Accessed: March, 2020.

64. References
• Romanowski B, Schwarz TF, Ferguson LM, Peters K, Dionne M,
Schulze K, Ramjattan B, Hillemanns P, Catteau G, Dobbelaere K,
Schuind A. Immunogenicity and safety of the HPV-16/18 AS04-
adjuvanted vaccine administered as a 2-dose schedule compared
to the licensed 3-dose schedule: Results from a randomized study.
Human vaccines. 2011 Dec 1;7(12):1374-86.
• https://gco.iarc.fr/today/data/factsheets/populations/288-
ghana-fact-sheets.pdf