Association between oropharyngeal cancers with known HPV and p16 status and cervical intraepithelial neoplasia: a Danish population-based study

Abstract

Background: Persistent infection with high-risk genotypes of human papillomavirus (HPV) is the main risk factor in the development of uterine cervical precancerous lesions and cervical cancer (CC), and cases of HPV-induced oropharyngeal squamous cell carcinoma (OPSCC) is increasing in the Western world. We investigated the association between HPV and p16 status and previous results of cervical examinations, including cytological and histological tests, in females with OPSCC. Material and Methods: We included females diagnosed with an OPSCC in Eastern Denmark from 2000 to 2014. OPSCCs were assessed for p16-overexpression and HPV DNA PCR. History of cervical tests was obtained from the Danish Pathology Registry. The cytology and histological results were categorized in accordance with the 2014 Bethesda System (TBS) and WHO. Hence, we divide the cervical results into two groups. Group I were negative for intraepithelial lesion or malignancy and group II had epithelial cell abnormalities and subdivided after increasingly neoplastic severity from A-D. Chi 2tests and Fischer's exact tests were performed to compare the two groups. Results: A total of 417 women with OPSCC were identified; 203 with HPV-positive tumors (49%) of which cervical cytology or histology were available in 172 women (85%). Among these, 22 (13%) patients had a cervical history of ! IIC. A total of 171 out of 214 women in the HPV-negative group (80%) were examined with cytology and 17 had a history of ! IIC. No significant difference in diagnoses of (pre)cancerous lesions between the OPSCC HPV-positive and negative groups were observed (v 2 test p ¼ .28, Fischer's exact test p ¼ .29). Conclusion: HPV status in oropharyngeal tumors was not correlated with a history of ! IIC in cervical examinations. The effect on cervical dysplasia may be masked by a higher incidence of smoking among the OPSCC HPV-negative group. ARTICLE HISTORY

Association of human papillomavirus related squamous cell carcinomas of the oropharynx and cervix

“…Some studies investigated smaller retrospective cohorts of women with OPSCC to identify their risk of CC [[22], [23], [24], [25]]. However, some lacked p16 status [22,25], while others stratified their data based on p16 status when available [23,24]. Skinner et al [22] studied a mixed small cohort of men and women (n = 143) with multiple potentially HPV-related cancers at different sites.…”

“…A recent Danish study [23] found no difference in the association between HPV/p16+ve OPSCC and CC. However, they identified 1.35 greater odds of developing HPV/p16+ve OPSCC in women with high grade squamous cell abnormalities or CC.…”

“…Several studies have looked at the association between OPSCC and CC [[16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26]]. Most of these studies included women with CC as their cohorts, they lacked p16 data and therefore included HNC sites that are non-HPV related [[16], [17], [18], [19], [20], [21], [22]].…”

Women with cervical cancer precursor lesions: a high-risk group for human papillomavirus (HPV)-related oropharyngeal cancer?

“…In this issue of Acta Oncologica, Christensen et al report the results of an interesting Danish study aiming to further elucidate the potential association between cervical abnormalities and subsequent HPV-related OPSCC [16]. The authors included all female OPSCC patients in Eastern Denmark during 2000-2014 (n = 417) and determined the HPV and p16 status of the tumours.…”

“…Smoking is a well-known risk factor for both cervical cancer and OPSCC [3]. The data of Christensen et al [16] indicate that the association between HPV status in OPSCC and history of cervical abnormalities may be more pronounced in smokers than in non-smokers. However, the statistical power was limited, and larger studies are needed to further disentangle the impact of smoking on risk of OPSCC in women with previous highgrade CIN. In summary, some studies suggest that women with a history of cervical premalignancies are at increased risk of OPSCC [9,10] and also non-cervical anogenital cancers [10,12,13,17].…”