Dr Chintana HapuachchigeMBBS, MD, MRCOG

Consultant Gynaecological Oncologist

National Cancer Institute, Maharagama

01.09.2017

Prevention of Cervical Cancer

and where we are and

the way forwards

Father of Gynae- Oncology in Sri Lanka

National Cancer Institute

Sri Lanka

• Established in 1958 (50 years old)

• Average 15000 patients referred annually

• 60% female cancers - 40% male cancers

• 850 in ward patients ( One of the largest in the World)

• 100 children

• 700 patients attend clinics every day

• Referrals from all parts of country including North

and East

Cervical Cancer

Cervical cancer

• is caused by the sexually transmitted HPV,

(A preventable non-communicable disease )

• Almost all sexually active individuals will be

infected with HPV at some point in their lives and

some may be repeatedly infected.

• The peak time for infection is shortly after becoming

sexual active.

Common early symptoms

• Inter-menstrual bleeding

• post-menopausal bleeding

• Post-coital bleeding

• Abnormal vaginal bleeding

• An unusual vaginal discharge

• Excessive sero-purulent discharge

Cause

• Human Papilloma Virus infection (99.7%) [essential factor]

• Other co-factors

– Multiple sexual partners (Female commercial sex workers)

– Early age at coitarche

– Giving birth at very young age

– Multiple pregnancies

– Presence of other sexually transmitted infections

– Weakened immune system (HIV / organ Transplant )

– Smoking

– Long term use of contraceptive pills more than 10 years

– Low socio economic status

HPV types and disease association

Natural history of HPV cervical

infection

• 90% would clear it within 6-14 months.

• 10% become latent infection(due to viral

persistence)

• 10-20% of these latent infections will progress to a productive infection.

• 10% of women with a productive infection and very rarely latent infection will progress to transforming infection - cancer

Normal cervix

HPV related changes

Low grade SIL(CIN1)

High Grade SIL(CIN 2/3 and CIS

Invasive Cancer

2/3 regress

within 2-3 yrs

HPV Infection

High risk HPV

Types-

16,18,33,45High Risk HPV Types16,18,31,33,45

1/3 progress

within 3-4 yrs

30-70%

progress within

10yrs

Prevention

• Primary prevention - Lifestyle factors

HPV vaccine

HPV vaccination

• was introduced in the UK in September 2008

• By 2014, 2.3 million girls had been vaccinated in England

• coverage of 85% of the eligible population.

• Cross protection against less common HPV types.

• vaccines work best if administered prior to exposure to HPV

• vaccines require 2/ 3 doses, administered over 6 months

• At present the vaccine is thought to be efficacious for at least 8-9 years after the initial regime

• still recommended to have cervical cancer screening.

HPV vaccine types

• Bivalent HPV (HPV2) vaccine (for prevention of 70% of cervical cancer cases)

– Contains HPV types 16 and 18 (high risk)

– Approved for females aged 10 through 25 years

• Quadrivalent HPV (HPV4) vaccine (for prevention of 70% of cervical cancer cases)

– Contains HPV types 16 and 18 (high risk) and types 6 and 11 (low risk)

– Approved for females and males aged 9 through 26

Years

• Ninevalent HPV vaccine (9v HPV) (for prevention of 90% of cervical cancers)

- Contains HPV geno types 6, 11, 16, 18, 31, 33, 45, 52, and 58

- for use in girls and young women 9 to 26 years of age

- for the prevention of cervical, vulvar, vaginal, and anal cancers

- pre-cancerous or dysplastic lesions genital warts caused by HPV types 6 and 11

After vaccination

Secondary Prevention

or Screening

• Conventional (Pap) 1940

• liquid based cytology (LBC) 2004

• LBC with concomitant use of HPV testing 2013 for

‘Triage’ in women with borderline and low-grade

dyskaryosis and also as ‘Test of Cure’ following

treatment for CIN and CGIN.

• Visual inspection with Acetic Acid(VIA)

• Coverage in Sri Lanka 30%

Future of screening

• UK National Screening Committee recommended in January

2016 that HPV primary screening should be adopted by the

screening programme.

• HPV-based primary screening provides a 60-70% greater

protection against cervical carcinomas compared with LBC.

• HPV testing in more sensitive and has a very high negative

predictive value.

• It is cost-effective as it will save more lives and reduce costs

through extension of screening intervals.

Conventional cytology: Pap smear

.

a) Combined spatula

b) Endocervical brush

c) Cervical broom

Cyto brush

Referral criteria for colposcopy

• Hans Hinselmann first described this method in 1925

• All smears with HGSIL

• Two consecutive LGSIL smears

• Following treatment of pre malignant and malignant

lesions

Cervical changes

Normal variations-colposcopic view

Post menopausal

Cervical ectropion

CERVICAL TRANSFORMATION ZONE

NORMAL PREINVASIVE

Pre malignant lesions- Cervix

LGSIL

HGSIL

Abnormal cervix

Treatment of CIN

• CIN can be treated by ablative and excisional

techniques. Both have a cure rate of >90% and there

is no difference between the two techniques when it

comes to treating and eradicating CIN.

• Both methods aim to remove the transformation zone

and the lesion. All techniques used should remove

tissue to a depth 7e10 mm so as to ensure eradication

of CIN that may involve the gland crypt.

Treatment of CIN

• Ablative techniques destroy the cervical epithelium. Hence accurate pre-treatment punch biopsy samples are required to exclude invasion prior to ablative treatment.

• Ablative techniques

Various ablative techniques are available such as

1. Cryocautery,

2.Cold Coagulation,

3. Laser Ablation and

4. Diathermy Ablation.

Cryocautery is the commonest ablative technique used.

Treatment of CIN

• Excisional techniques

• Various excisional techniques are available. These

include LLETZ/Loop Biopsy, NETZ/SWETZ

(Needle/Straight Wire Exci- sion of Transformation

Zone), Cold Knife Conization, Laser Conisation .

• Hysterectomy.

2.Loop excision(LLETZ)

3.Cone biopsy

Where we are

Cervical cancer

• Cervical cancer is the second most common

cancer in women worldwide.

• 530 000 new cervical cancer cases diagnosed every year.

• Globally 1.4 million women were living with cervical cancer (2012)

• Globally most affected age group – 30-55 years causing grave

morbidity and mortality to women

• Every year more than 270 000 women die from cervical cancer,

more than 85% of these deaths are in low and middle income

countries.

National Cancer Institute

Sri Lanka

Annually

• 8000 new cancer patients registered

• 1200 – oral cancer

• 1100 – breast cancer

• 500-600 – cervical cancer

National Cancer Control Programme, Cancer Incidence data 2007,

2nd

commonest female cancers – 10% of all female cancers are cervical cancer (2008)

This translates to nearly 850-950 cervical cancer cases annually (hospital data)

500- 600 cases in Maharagama

Situation inSri Lanka

41Source: National Cancer Control Programme

Cervical Cancer : age distribution in Sri Lanka - 2009

Cervical Cancer Screening Programme –

Well Woman Clinics

42Annual Report on Family Health 2013, Family Health Bureau, Ministry of health , Sri Lanka

Total Pap smears at WWC :

132,385 (2013)

Number of Well Woman Clinics

Percentage of women attending Well Woman

Clinics

Percentage of 35 year age cohort screened

with Pap smear

Pap smear statistics

• WWC• National Cancer Control programme : 2000/year

[reading at FHB lab]

• STD clinic: 1000-1500 per year [Annual Report 2015]

• Government Hospitals: Gynecological wards and

clinics- published data not available

• Private sector /semi Government/ NGO-

published data not available

47

number needed to screen to

prevent one cervical

cancer case1130 [>35

years]

Minimum unit cost of Pap smear

screening Rs. 308/-

Rs. 348,040/-Prevention of reported

annual case load of 850-900 cases : 313 m SLR/yr

[Excludes treatment of screen detected cases]

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Cost for Pap smear screening

Total invasive cervical cancer detected at pap smear screening 1.15/2000

Sri lankan guidelines

• Sexually active above age of 35

• Or 5 years after 1st coitarche

• Only conventional Pap test

• LBC / HPV testing in Private sector

Why still common?

• widely available screening centers island-wide

– But coverage is low 30-40%

– Lack of awareness among general public

– No proper referral and feed back system

– No proper follow up system

• HPV vaccine was Introduced under EPI programme in 2017

A woman should not die or suffer

from cervical cancer when it is

preventable!

54

Dr. Deepa Gamage-Community Medicine Consultant

Treatment follow-up

• Patients after CIN treatment remain at risk of

recurrent disease. The risk of a future cancer is

approximately 4-5 times that of the background risk

and usually due to poor compliance with follow up.

• Majority of recurrences are usually detected within 24

months of treatment.

• Other factors that contribute to the risk of treatment

failure include age >40 years, high-grade lesions,

glandular lesions and positive treatment margins.

HPV test of cure

• After treatment of all grades of CIN women are invited for screening after 6 months for LBC and HPV testing.

• HPV testing has a higher sensitivity and negative predictive value compared with cytology or colposcopy alone in identifying residual/recur-rent disease.

• HPV testing in addition to LBC allows early return to routine recall if these tests are negative at 6 months.

HPV test of cure

• CGIN treated patients are at higher risk of

recurrent disease. If the excision was incomplete,

these women should be followed up with cytology

and colposcopy at 6 months, 12 months and then

annually for another 9 years.

• If excision was complete then women should be

offered LBC and HPV testing at 6 and 18 months

and can be returned to normal recall if these are

negative.

Future of colposcopy

• DySIS is a digital video colposcope that also uses

dynamic spectral imaging to evaluate the ‘whitening’

effect of acetic acid on the epithelium

• The Niris Imaging System uses optical coherence

tomography as an adjunct to a standard colposcope. It

uses near-infrared light

• NICE have recommended that DySIS is a clinically

and cost- effective option, compared with standard

colposcopy

Annually• 266,000 deaths, and

85% are from developing countries

Without urgent action deaths due to cervical cancers are projected to rise by almost 25% over the next 10 years

Global mortality

Papillomavirus phylogenetic tree

• The alpha-papillomavirus genus of the papillomavirus phylogenetic tree is shown*

• Oncogenic types closely related to HPV 16 and 18 are highlighted

• HPV 16 is most closely related to HPV 31

• HPV 18 is most closely related to HPV 45

40

7 3242

3959

5544PCV113

11

673

34

61

27

2a57

328

1029

51

263053

56

66

RhPV1

70

18

45

583352

1635

31

Factors to be considered in secondary prevention

Increase Pap smear coverage

– Health care institutional demand/facilities

– Creating public awareness (Demand by women/ beneficiaries )

– Increasing accessibility and availability of services

Follow up of screen detected cases

– Adequate treatment opportunities & follow up

– Monitor and evaluation of programme impact

Feasibility/cost assessment for newer techniques : combine

methods

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