Recent Advances in the Prevention of

Cervical Cancer including the HPV

Vaccine
AKIN-TUNDE ADEMOLA ODUKOGBE
AKINYINKA O OMIGBODUN

OVARIAN CANCER SERVICE

GYNAECOLOGICAL ONCOLOGY
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY
UNIVERSITY COLLEGE HOSPITAL

IBADAN
 INTRODUCTION
Cancer of the cervix offers more opportunities (and
need) for its prevention compared to other female
genital tract malignancies:
1. The world’s second commonest cancer in females
2. Known aetiological factors: HPV present in over 97%
of cervical cancer cases
3. Cervix easily accessible to non – invasive methods
4. Cancer preceded by preinvasive lesions CIN I – III
5. Time from CIN to invasive cancer up to 15 years
6. The treatment of CIN can be conservative, is effective
and can be fertility sparing
7. Effective vaccines have been produced
 INTRODUCTION - 2
The burden of cervical cancer is mostly felt in the developing

countries with little human and material resources

Location Position of cervical Proportion / number of new Mortality
cancer among LGTCs cases in a year

World wide 1st of LGT cancers 493243 273505 annually

Developing world 1st of LGT cancers 4/5th of world’s new cases

Developed world 3rd or 4th of LGT cancers 1/5th of world’s new cases 2.3 per 100000

Nigeria, Africa 1st of LGT cancers 63.0% of LGT cancers 23.3 per 100000

Ghana, Africa 1st of LGT cancers 57.8% of LGT cancers 23.8 per 100000
 DIAGNOSIS OF CIN
Papanicolaou smear
- Conventional: (Negative, Inflammatory, CIN I – III)
- Bethesda: (Negative, Atypical lesions, LoSIL, HiSIL)
Colposcopy
Visual Inspection with Acetic acid, Lugol’s iodine
Cervicomicrograph and others
In the last decade several programs are aimed at
increasing screening in the
developing world: Nigeria – WHO
(promotion of VIA in rural areas), EXXON
Mobil (Cervical cytology)
 DIAGNOSIS OF CERVICAL CANCER
History
5
Physical examination
Ultrasound / CT / MRI / PET. Combinations
Examination under anaesthesia, and Staging
Biopsy and histology
Cystoscopy, Proctoscopy
Full blood count
Electrolytes, urea, uric acid and creatinine
Liver function tests
Chest Xray

NPMC Revision Course. August / September 2009.

PREVENTION – 1. Surgical treatment of CIN

Cone biopsy
- cold knife
- LASER
?Trachelectomy
Hysterectomy
Draw backs include perioperative
morbidity and mortality, localised
treatment and reproductive
consequences
PREVENTION – 2. Ablative treatment of CIN

Loop excisional electrocautery procedure (LEEP)

Cryotherapy

LASER therapy
 PREVENTION – 3. Chemopreventive agents
8
Intended for use in the prevention or reversal of cancer
initiation, promotion and progression
A. MICRONUTRIENTS

1. Folic acid supplementation:

Based on the finding that folic acid deficiency is
associated with cervical dysplasia
5 – 10mg orally daily
VERDICT: Not effective

NPMC Revision Course. August / September 2009.

 PREVENTION – 3. Chemopreventive agents
9
2. β carotene supplementation

Low β carotene level associated with cervical dysplasia

30mg orally daily
VERDICT: Not effective

NPMC Revision Course. August / September 2009.

 PREVENTION – 3. Chemopreventive agents
10
3. Indole – 3 – carbinol

Used in the treatment of HPV induced laryngeal

lesions
200mg / 400mg orally daily
VERDICT: Effective. For further trials

NPMC Revision Course. August / September 2009.

 PREVENTION – 3. Chemopreventive agents
11
B. VITAMIN A (RETINOIC ACID) AND NATURAL AND
SYNTHETIC DERIVATIVES
Retinoids are generally known to prevent normal
epithelial cells from becoming cancer cells

1. β – all – trans – retinoic acid

0.05 – 0.2% four times daily vaginally
VERDICT: Effective

NPMC Revision Course. August / September 2009.

 PREVENTION – 3. Chemopreventive agents
12
2. All – trans – retinoic acid
0.05 – 0.484% vaginally
VERDICT: Effective

3. 4 – hydroxy – phenylretinamide (4HPR)

Synthetic
200mg
VERDICT: No effect

NPMC Revision Course. August / September 2009.

 PREVENTION – 3. Chemopreventive agents
13
4. 9 – cis – retinoic acid (9 – CRA). Pan-retinoid
receptor agonist
25 – 50mg daily
VERDICT: No effect

5. 13 – cis – retinoic acid (13 – CRA)

1mg / kg / day
VERDICT: No effect

NPMC Revision Course. August / September 2009.

 PREVENTION – 3. Chemopreventive agents
14
C. POLYAMINE SYNTHESIS INHIBITORS

Polyamines play a role in epithelial cell function

1. α – Difluoromethylornithine (α DFMO)
0.06g / m2 – 1.0g / m2 daily
VERDICT: Effective

NPMC Revision Course. August / September 2009.

 PREVENTION – 3. Chemopreventive agents
15
D. CYCLOOXYGENASE – 2 – INHIBITORS

1. Celecoxib
200mg BD orally for 3 months
VERDICT: Effective

NPMC Revision Course. August / September 2009.

 PREVENTION – 4. Vaccines
16
> 50 HPV types infect genital tract with almost 20 of
them associated with cervical cancer
HPV – double stranded DNA virus, 8kb in length
Genome encodes six early genes (which affects host’s
cell – replication machinery) and two late genes
(encode for structural capsid proteins)
HPV produces two oncoproteins
- E6 binds to and degrades p53
- E7 binds to the retinoblastoma
protein

NPMC Revision Course. August / September 2009.

 PREVENTION – 4. Vaccines
17
A. PROPHYLACTIC VACCINES
They produce antibodies against HPV
1. Use of virus like particles (VLPs) vaccine (HPV 16)

2. Use of chimeric VLPs vaccine (HPV 16)

3. Use of bivalent vaccine (HPV 16, 18)

4. Quadrivalent vaccine (HPV 6, 11, 16, 18)

NPMC Revision Course. August / September 2009.

 PREVENTION – 4. Vaccines
18
B. THERAPEUTIC VACCINES
Cell mediated immunity is important in controlling
HPV diseases as shown by their proliferation in
transplant and HIV patients
These vaccines produce T cells which are able to
eliminate cells infected with HPV
No effective culturing system for HPV
Oncogenicity precludes use of
attenuated virus

NPMC Revision Course. August / September 2009.

 PREVENTION – 4. Vaccines

1. HPV peptide vaccines 19

2. DNA vaccines
 Cause both humoral and T cell responses

3. Viral vectors: live recombinant vaccina virus

expressing the E6 and E7 proteins of HPV 16 and 18
4. Dendritic cell (DC) based tumour vaccines

NPMC Revision Course. August / September 2009.

 PREVENTION – 4. Vaccines
20

ISSUES RELATED TO VACCINATION

1. Number of types covered: bivalent, quadrivalent

(covers 75% of infections)
2. Route of delivery: subcutaneous / mucosally
3. Point in menstrual cycle
4. Age of vaccination: 9 – 12 years (prophylactic vaccines)
5. Parents’ views since HPV is sex – related
6. Use in healthy population

NPMC Revision Course. August / September 2009.

 PREVENTION – 4. Vaccines
21

7. Vaccination of men (HPV: penile cancer, reservoir)

8. Logistics
9. Costs: N9000 per vaccine in Nigeria, £80 in UK
10. Concurrent screening using Pap smear, etc
11. Schedule: 0, 1 and 6th months
12. Duration: 5 years
13. Revaccination?: if so, when?

NPMC Revision Course. August / September 2009.

 HPV VACCINATION IN THE UK

Commenced September 2008

Part of school vaccination programme
Offered to all 12 year old girls
Not dependent on HPV status
State funded
Bivalent HPV 16 and 18 – Cervarix
Quadrivalent HPV 6, 11, 16 and 18 – Gardasil
Efficacy: per protocol 98%
Acceptance: 77.8% 1st dose, 61.7%
2nd dose
 PREVENTION – 5. Other strategies

Late coitarche

Consistent and correct use of condom

Avoidance of multiple sex partners (Note: 1% of

female newborns have genital tract HPV infection)
 REFERENCES
1. Materials from presentations at Gynaecological Oncology Symposium, Pride
Park Stadium, Derby, England. 27 February 2009. Gill Turner, Summi Abdul, A.
Hitchcock, M. Persic, John Tidy
2. Nkyekyer K (2000). Pattern of gynaecological cancers in Ghana. East Afr Med J
77: 534 – 8
3. Basile S, Anglioli R, Manci N, Palaia I, Plotti F and Benedetti Panici P (2006).
Gynecological cancers in developing countries: the challenge of chemotherapy in
low-resource setting. Int J Gynecol Cancer 16: 1491 – 1497
4. Odukogbe AA, Adebamowo CA, Ola B et al (2004). Ovarian cancer in Ibadan:
characteristics and management. J Obstet Gynaecol 24: 294 – 7
5. Bell MC and Alvarez RD (2005). Chemoprevention and vaccines: a review of the
nonsurgical options for the treatment of cervical
dysplasia. Int J Gynecol Cancer 15: 4 – 12
6. Trimble EL, Davis J, Disaia P
et al (2007). Clinical trials in gynecological
cancer. Int
J Gynecol Cancer 17: 547 - 556
THANK 25

YOU
NPMC Revision Course. August / September 2009.