1. Picture taken from leaflet of Wartec: Podophyllotoxin

2. Singular: condyloma acuminatum Plural: condylomata acuminata

3. Excellent HPV DNA Test by the Mendel Center DNA Extraction
Sample: Cervical washing with normal saline (easy sampling, stable sample up to several days non-refrigerated, can measure viral load per gram wet weight)
DNA Extraction
PCR, very sensitive
High Resolution typing by restriction digestion
European HPV DNA test External Quality Assurance Scheme (EHEQAS) coordinated by Dr Pavlos Neophytou, Mendel center for Biomedical Sciences

4. Our Measurement of HPV DNA viral Load correlates well with clinical results

5. HPV typing by RFLP HPV53 + HPV 53 HPV 66 HPV 66
High resolution typing including cases of co-infection

6. DNΑ Sequencing
We have identified:
1 novel HPV type (>10% different from all known types)
4 subtypes HPV (2-10% different)
10 HPV variants (<2% different)
4 human sequences amplified by HPV-specific primers. This allows us to eliminate false-positives, hence
Test Specificity=100%
(Dr Arif A. Albayrak and Dr Serap K. Uluçay are co-authors of the electronic HPV DNA and protein files listed in the European Bioinformatics Institute databases)

7. Epidemiological Study in Cypriot Women
Years
Aims
Levels of Infection and types in Greek-Cypriot and Turkish-Cypriot women
Study of possible factors of risk: sexual behaviour, smoking, history of other STD etc.

8. Cypriots examined by place of residence

9. By age and community

10. Good Cross-section of population
521 Greek-Cypriot (0.3% των 180,000 aged 18-71), mean age=37 [mainly Nicosia and Paphos districts]
187 Turkish-Cypriots (0.5% των 40,000 aged 21-65), mean age=41 [mainly Famagusta district including Iskele]

11. Factors of risk By dividing women in 3 groups:
High Risk (pathological Pap test, condylomata)
Moderate Risk (Multiple sexual partners >1, smoking, other STD)
Low risk
In Greek-Cypriots HPV-infection is significanlty associated with the above grouping (p<0.01)
In TC no statistically significant differences

12. General population infection rate
Women of low-moderate risk are those who never had a pathological Pap test (ASCUS, CIN) and never had condylomata
The levels of infection in these women were statistically different:
15% GC, 27% TC

13. Population Screening
The mean interval between Pap tests was determined as the inverse of (no. of Pap tests) / (age – age at first coitus)
A significant difference was found:
GC: One Pap test every 2 years
TC: One Pap test every 14 years

14. Condylomata
Levels:
GC (without a pathological Pap test): 3%
GC (with a pathological Pap test): 10%
TC (without a pathological Pap test): 8%
TC (with a pathological Pap test): 14%
HPV infection is related with a history of condylomata in GC and in TC (p<0.01).

15. HPV types in GC
Of 521 GC, 145 were HPV-positive, of which 31 were co-infected by 2 or more types (21%).
Most frequent types: HPV6 (19%), HPV16 (15%), HPV66 (13%), HPV53 (11%), HPV31 (5%)
In total 29 types were detected, including the 2 novel types discovered in Cyprus.

16. HPV types in ΤC
Of 187 TC, 53 were HPV-positive, of which 8 were coinfected by 2 or more types (15%).
Most frequent types: HPV58 (42%), HPV66 (18%), HPV11 (11%).
In total detected 12 HPV types.

17. No. of Sexual Partners in HPV +ve women

18. No. of Sexual Partners
In GC it was found that women with MSP (more than one) had a significantly higher risk of:
Being HPV-infected (p<0.001)
Having a history of CIN (p<0.001)
Having condylomata (p<0.001)
In TC only found a significant difference only as regards the history of condylomata(p<0.025), (the number of women with pathological Pap test examined was small)

19. Smoking
In Greek Cypriots smokers (26% of the population) had a significantly higher risk:
Of being HPV -infected (p<0.001)
Of having CIN (p<0.001)
No relationship with condylomata
In TC no statisticallly significant difference was found (smokers: 36% of population)

20. Our populations are getting worse!
54% of GC women under 30 years had MSP in comparison to 18% of women over 30 years (p<0.001).
41% of GC women under 30 years were smokers in comparison to 23% of women over 30 years (p<0.025).
IN TC observe an increase in percent of women with MSP in younger ages but no increase in smokers

21. History of other STD
3% of GC και 4% of TC had a history of other STD (herpes, Chlamydia, gonorhea). Noone had a history of syphilis.
In GC there was a statistically significant association of history of STD with HPV infection (p<0.05).
In TC no statistically significant difference.

22. Age at first coitus (AFC)
Mean AFC was 21 years in both communities.
Women with AFC under 16 was less than 2% in both communities.
Young age at AFC is not a big factor of risk in Cyprus yet:
AFC = 19 for women under 30 years (4% AFC<16)
AFC= 21 for women over 30 years (2% AFC<16)
In Scandinavia >50%!

23. Conclusions
Levels of infection in general low-modarate risk populations: GC (55/355)= 15%, TC (43/162 =) 27%
In TC no important risk factors were found, the main problem is the low frequency of undergoing Pap tests, and therefore the application of the HPV DNA test as screening tool in the Turkish-Cypriot community will contribute significantly to the lowering of the burden from cervical neoplasia and cancer. Given the rate of general population infection (27%) it is suggested that TC women should undergo an HPV DNA test once every 3 years.

24. Conclusions
In GC 2 important risk factors allow us to divide the population into subgroups:
Low risk (non-smokers and one SP): 8%
Moderate risk (smoker or SP>1): %
It is suggested that low risk GC women should undergo screening by HPV DNA test once every 4 years and moderate risk women undergo screening by HPV DNA test once every 2 years.

25. Factors of risk
Multiple sexual partners, smoking, low age at first coitus
Penetrative sex is not a pre-requisite for infection:
Condom does not provide absolute protection from HPV
Lesbians and virgins can get infected by HPV
Babies infected by their mother at birth can get condylomata in the larynx

26. Factors of risk
HPV infection may remain latent for many years. Hence women who are not sexually active for a certain period must continue to undergo regular screening (HPV DNA test and/or Pap test)

27. Protection Measures Use a condom Population screening HPV vaccines
Partial Protection from HPV
Helps HPV regression in HPV infected couples
Complete protection from other STD (AIDS)
Population screening
HPV DNA test (primary test)
Pap test (secondary test)
HPV vaccines