Human Papillomavirus (HPV) types in Cervical Cancer in Jordan Maher Sughayer M.D
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Human Papillomavirus (HPV) types in Cervical Cancer in Jordan
Maher Sughayer M.D
Full Member and Chairman, Pathology Dept.
King Hussein Cancer CenterAmman, Jordan
An-Najah University, Faculty of Medicine Conference, Oct. 10, 2009
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*Markowitz; MMWR 23/3/07
Introduction
• Genital HPV is the most common STD in the United States* & probably in the world
• 6.2 million people are newly infected/year in the US alone.
• About 100 HPV types are identified of which 40 infect the genital regions.
• Low-risk types (6, 11): LSIL, genital warts.• High-risk types: HSIL, cervical cancer.
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High-Risk Types
• Include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 73, and 82 : cause invasive cervical cancer, LSIL, HSIL and other anogenital cancers.
• Found in 99.7% of ca cervix.• HR HPV is necessary but not
sufficient for ca cervix.
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Agosti, NEJM, 356, 2007
Cervical Cancer
• The 2nd most common cancer in women worldwide.
• 493,000 new cases diagnosed annually.• Causing 274,000 deaths each year:
80% of which in the developing world.• The largest single cause of years of life
lost to cancer in the developing world.
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Agosti, NEJM. 356, May 10, 2007
Incidence Rates and Proportions caused by types 16/18
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Cervical Cancer in Jordan
• In 2003 Jordan Cancer Registry: 1735 cases of cancer in women.
• Cervical cancer cases: 41, not among the ten most common cancers in women.
• In contrast breast cancer cases: 551.• HPV types: unknown.
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Worldwide HPV Types in Cervical Cancer: The Impact of the Vaccine
• Several meta-analyses published on HPV types from all over the world (Munoz, Clifford, Clifford and finally Smith, 2007) to predict the impact of the new HPV vaccines.
• And to study regional variation for possible future modification.
• Smith’s meta-analysis: Int. J. Cancer, 2007
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Meta-analysis Findings: Minor Regional Differences
• In 14,595 cases: HPV 16 most common, 18 second and 16/18: 74-77% in North America, Europe, Australia and 65-70% in the rest of the world.
• The next most common types: 31, 33, 35, 45, 52 and 58, in all continents but not in the same order
• 58 and 52 more important in Asia, 56 in Europe.
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Smith, Int. J. Cancer, 2007
Number of Cases of Cervical Cancer with Available HPV Typing
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Multiple Infections with High-Risk HPV Types in Invasive Cervical Cancer• Cuschieri (J Clin Pthol 2004): 40% of
HSIL cases have multiple HR HPV types.
• Lai (Int J Cancer 2007): 18% of scc cases have multiple infections.
• Gargiulo (Virus Res. 2007): 49% have multiple infections.
• The effect of multiple infections on progression to cancer is not clear.
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HPV Typing in Cervical Cancer in Jordan
• Objective: To determine HPV types involved in invasive cervical cancer in Jordan.
This is necessary to establish a base line and to check for any regional differences in HPV types in Jordan “in case a vaccine is to be considered?”
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Methods
• The archives of the Pathology department were searched for cases of ICC.
• Cases with available paraffin blocks were used for the study.
• DNA was extracted using a commercially available kit (Extra DNA
Tissue kit, Sacace Biotechnologies, Italy).
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Methods
• Adequacy and integrity of extracted DNA were assessed (spectrophotometry and PCR for GAPDH gene).
• Multiplex PCR using a commercially available kit (HPV High Risk Typing, Sacace Biotechnologies, Italy).
• 4 mixes (types 16, 31, 33, 35), (18, 39, 45, 59), (52, 56, 58, 66) and for some cases (6, 11).
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• Electrophoresis and band identification using DNA ladder. Results were invalidated if internal control (B-globin gene) was absent.
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Results
• 48 cases with paraffin blocks were identified.
• One adenocarcinoma, one adenosquamous, 46 sq. cell ca.
• Age: range 37-80. median age group: 44-49 years.
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Age Distribution
0
2
4
6
8
10
12
14
35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84
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HPV Type Distribution
• Successful DNA extraction was achieved in 41 cases.
• 7 cases failed to produce adequate DNA.
The reasons: old blocks, poorly processed/fixed tissue samples (referral material), small consumed biopsies.
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HPV TYPE DISTRIBUTION
HPV Type Number %
16 28 68.3
18 10 24.4
39 4 9.8
56 4 9.8
45 3 7.3
52 3 7.3
33 2 4.9
31 1 2.4
35 1 2.4
58 1 2.4
59 1 2.4
66 0 0
6 0 0
11 0 0
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HPV Type Prevalence
0
10
20
30
40
50
60
70
16 18 39 56 45 52 33 31 35 58 59 66 6 11
%
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• Types 16/18 found in 75.6% of cases.• Multiple infections (2 or 3 types)
were found in 14 cases representing 34% of all cases.
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Conclusions
• Types 16/18 are the most common types in cervical cancer in Jordan and are responsible for 75% of cases.
• Other types (39, 56, 45, 52, 33, 31, 35, 58, 59) are responsible for 25%.
• The relative importance of non 16/18 types is slightly different from reported studies: 39 and 56 appear more important than other minor types But…
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• The number of cases (non 16/18) is small and more studies are needed.
• Multiple infections are common similar to previously reported studies.
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Thank You
• Tasnim Dayeh• Suzan Oraibi• Mai Abu-Taha• Mohamad Abdel-Hadi• Lian Otay