FC 04-03HUMAN PAPILLOMAVIRUS NEGATIVITY: WORSE PROGNOSIS IN INVASIVE CERVICAL CANCER

02. Epidemiology and natural history
J. Lei 1, A. Ploner 1, C. Lagheden 2, C. Eklund 2, S. Nordqvist Kleppe 3, B. Andrae 4, K. Sundström 3, M. Elfström 5, J. Dillner 3, P. Sparén 1.
1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Sweden), 2Department of Laboratory Medicine, Karolinska Institutet, Stockholm (Sweden), 3Department of Medical Epidemiology and Biostatistics/Department of Laboratory Medicine, Karolinska Institutet, Stockholm (Sweden), 4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm/Center for Research and Development, Uppsala University/Region of Gävleborg (Sweden), 5Department of Laboratory Medicine, Karolinska Institutet/Regional Cancer Center Stockholm-Gotland, Stockholm (Sweden)

Background / Objectives

HPV-negativity has been reported to be associated with worse prognosis for some HPV-associated cancers. Whether detectability of HPV is related to prognosis of invasive cervical cancer is more controversial and would need very large studies to be clearly answered.


Methods

We identified all cervical cancers diagnosed in Sweden during a 10 year period (2002-2011; 4254 confirmed cases), requested the archival blocks and subjected them to HPV genotyping using general primers targeting the L1 region, followed by typing with Luminex for 14 high risk types including 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 and non-high risk types including 6, 11, 26, 30, 40, 42, 43, 53, 54, 61, 67, 69, 70, 73, 74, 81, 82, 83, 86, 87, 89, 90, and 91). Blocks from 2848 cases were retrieved and analyzed, and were prospectively followed up from date of cancer diagnosis to 31 December, 2015, migration from Sweden, or death, whichever occurred first. Five year relative survival ratios were calculated and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated by a Poisson model, adjusted for age at cancer diagnosis, FIGO (International Federation of Gynecology and Obstetrics) stage and education.


Results

The HPV L1 region was detected among 2368 (83.1%) of all cases. For HPV L1-negative women, the 5-year relative survival ratio was 0.54 (95% CI, 0.49-0.59) and for women with HPV L1-positive tumours 0.74 (95% CI, 0.72-0.76), yielding a crude EHR of 0.45 (95% CI, 0.38-0.53) and adjusted EHR of 0.53 (95% CI, 0.45-0.62). The 5-year age-specific adjusted EHRs for women with HPV L1-positive tumor were 0.53 (95% CI, 0.32-0.88) at age 30-44, 0.69 (95% CI, 0.48-0.99) at age 45-59, 0.59 (95% CI, 0.44-0.79) at age 60-74 and 0.40 (95% CI, 0.30-0.52) at age 74 and above respectively compared to women with negative tumours. Compared to negative tumours in each stage, the adjusted EHRs of HPV L1-positive tumours were IA: 0.67 (95% CI, 0.08-5.69), IB: 0.61 (95% CI, 0.41-0.91), II: 0.47 (95% CI, 0.34-0.65) and III+: 0.53 (95% CI, 0.43-0.66). For squamous cell carcinoma the adjusted EHR of HPV L1 positive tumours was 0.57 (95% CI, 0.46-0.70), while for adenocarcinoma it was 0.52 (95% CI, 0.36-0.74).

 


Conclusion

Women with tumors negative for HPV L1 have much worse prognosis than women with HPV L1-positive tumours, irrespective of age, clinical stage and histological tumour type.


References