Prevalence of human

papillomavirus positive

oropharyngeal cancer in New

ZealandLucas-Roxburgh R, Benschop J, Lockett B, Williams R, Van den

Heever U & Howe L

HPV in HNSCC

• HNSCC include cancers of oral cavity, oropharynx, larynx, hypopharynx

• In 2005 IARC concluded HPV 16 had evidence for carcinogenicity in oral cavity and oropharynx

• Dramatic increase seen in developed countries in last few decades

HPV + vs HPV - HNSCC

HPV positive

• Younger (40-59)• Non-smoker• Non / light drinker• Consistent associations with

sexual behaviours & oral sex• Site: Oropharynx, tonsils, base

of tongue• 5 year survival: improved

HPV negative

• Older (over 60)• Smoker• Heavy drinker• Sexual behaviours show no

association• Site: Oral cavity and larynx

• 5 year survival: poor

HPV positive OPC cases

23% - 1970s93% - 2006-07

16% - 1984-8972% - 2000-04

19% - 1987-9047% - 2001-05

The research project

To determine the prevalence of and genotypes associated with HPV positive oropharyngeal cancer in New Zealand.

Methods – case identification

• 621 cases identified through cancer registry data

• Consent obtained from any patient still living

– 303 consents sent, 157 returned

– 52% response rate

• 388 cases requested from laboratories

Methods – Lab tests

– p16 IHC

– Beta-globin PCR (DNA quality)

– Real time PCR + melt analysis for HPV type

16.

– GP5+/6+ PCR (presence of HPV) + melt

analysis

Results – study populationNational dataset

(n=621)

Study population

(n=267)

p-value

Mean age at diagnosis 59.2 years 60.1 years 0.30Sex : Male

Female

492 (79.2%)

129 (20.8%)

209 (78.3%)

58 (21.7%)0.82

Ethnicity: NZ European

NZ Maori

Other

Not stated

427 (68.8%)

65 (10.5%)

118 (19.0%)

11 (1.7%)

190 (71.2%)

29 (10.9%)

45 (16.9%)

3 (1.0%)

0.77

Timeframe: 1996-98

2003-05

2010-12

113 (18.2%)

185 (29.8%)

323 (52.0%)

51 (19.1%)

83 (31.1%)

133 (49.8%)

0.83

Deceased

Living

277 (44.6%)

344 (55.4%)

158 (59.2%)

109 (40.8%)<0.01

Results – p16

Positive Focally positive Negative58.4% (156/267) 7.9% (21/267) 27.3% (73/267)

Remaining 6.4% (17/267) either no tumour present or insufficient material.

Results - beta-globin

• DNA extracted from 224 samples.

• 4.0% (9/224) excluded due to a lack of

amplifiable DNA.

Melt curve of beta globin qPCR. Positive samples shown with Tm of 81.0 °C (±1.0 °C).

Results - HPV 16 qPCR

• Assay capable of detecting 26 copies of

the HPV 16 E6 gene target sequence.

• HPV 16 detected

in 74.4% (160/215)

of cases.Melt curve of HPV 16 qPCR. Positive samples shown with

Tm of 77.6 °C (±1.0 °C).

Results - GP5+/6+ qPCR

• 17 cases p16 positive/focally positive and HPV 16 negative.

• 82.4% (14/17) negative and 17.6% (3/17) positive.

• HrHPV confirmed by sequencing in two cases, one case each of HPV 33 and 35. Melt curve of GP5+/6+ qPCR. Positive samples

shown with Tm in the range of 76.0 – 81.0 °C

Results

• Positive = positive by p16, and HPV 16

qPCR / sequencing.

• Overall prevalence of HPV positive OPC:

77.9% (95% CI: 71.1 – 83.5%).

• HPV 16 accounted for 98.5% (132/134).

ResultsVariable Odds Ratio 95% CI P value

Age ≤60 REF

≥61 0.55 0.33-0.99 0.05

Sex Female REF

Male 1.36 0.68-2.66 0.38

Ethnicity NZ European REF

NZ Maori 1.49 0.55-4.52 0.45

Other 1.14 0.53-2.53 0.74

Timeframe 1996-98 REF

2003-05 1.76 0.83-3.81 0.14

2010-12 5.65 2.60-12.30 <0.01

Conclusions

• Increase in HPV positive cases, from

61.9% in 1996-98 to 87.5% in 2010-12.

• In NZ the number of HPV positive OPC

cases will soon equal the number of

cervical cancer cases.

Vaccination and OPC

• Decreases in CIN, and genital warts seen

since Gardasil® introduction.

• Vaccine will likely prevent OPC

– Estimated VE of 93·3%

New Zealand dataCervical cancer Oropharyngeal cancer

Case numbers (2012)1 116 126

% HPV attributable 100% 88%

Number HPV attributable 116 111

Vaccine preventable –Gardasil® 4 82 (71%) 2 109 (98.5%)

Vaccine preventable –Gardasil® 9 104 (90%)2 110 (99.3%)

1 NCSP annual report (2012). Retrieved August 30, 2017 from:https://www.nsu.govt.nz/system/files/page/annual_report_2012.pdf

2de Sanjose, S., Quint, W. G. V., Alemany, L., Geraets, D. T., Klaustermeier, J. E., Lloveras, B., et al (2010). Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. The Lancet Oncology 11, 1048-1056.

Thank you!