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

*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.

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.

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.

Agosti, NEJM. 356, May 10, 2007

Incidence Rates and Proportions caused by types 16/18

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.

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

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.

Smith, Int. J. Cancer, 2007

Number of Cases of Cervical Cancer with Available HPV Typing

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.

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?”

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).

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).

• Electrophoresis and band identification using DNA ladder. Results were invalidated if internal control (B-globin gene) was absent.

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.

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

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.

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

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

%

• 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.

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…

• The number of cases (non 16/18) is small and more studies are needed.

• Multiple infections are common similar to previously reported studies.

Thank You

• Tasnim Dayeh• Suzan Oraibi• Mai Abu-Taha• Mohamad Abdel-Hadi• Lian Otay