Prevalence of HPV-DNA and E6 mRNA in lung cancer of HIV-infected patients

Abstract

HIV-infected individuals could be at a greater risk for developing lung cancer than the general population due to the higher prevalence in the former of human papillomavirus (HPV) in the oral cavity and higher smoking rates. Our aim was to assess HPV prevalence and E6 viral oncogene transcription in lung cancer samples from HIV-infected individuals. This was a single-center, retrospective study of a cohort of HIV-1-infected patients diagnosed with and treated for lung cancer. Pathological lung samples archived as smears or formalin-fixed paraffin-embedded blocks were subjected to HPV genotyping, detection of human p16 protein and assessment for HPV E6 mRNA expression. Lung cancer samples from 41 patients were studied, including squamous cell carcinoma (32%), adenocarcinoma (34%), non-small cell cancer (27%), and small cell cancer (7%). HPV DNA was detected in 23 out of 41 (56%, 95% CI 41–70%) of samples and high-risk (HR)-HPV types were detected in 16 out of 41 (39%, 95% CI 26–54%), HPV-16 being the most prevalent [13/16 (81.3%, 95% CI 57.0–93%]. In samples with sufficient material left: expression of p16 was detected in 3 out of 10 (30%) of HR-HPV DNA-positive tumors and in 3 out of 7 (43%) of the negative ones; and E6 mRNA was detected in 2 out of 10 (20%) of HPV-16-positive samples (squamous lung cancers). These two patients had a background of a previous HPV-related neoplasia and smoking. HR-HPV DNA detection was prevalent in lung cancers in HIV-infected patients. However, viral oncogene expression was limited to patients with previous HPV-related cancers.

Lung Cancer Presents at a Younger Age and Is Less Likely to be Curable in People Living with HIV

“…The human papillomavirus (HPV) is a known direct carcinogen which has been shown to have a higher prevalence at various sites in PLHIV [13]. In a study by Sirera et al [14], both HPV DNA (56%) and high risk-HPV DNA (39%) were detected in biopsy specimens of HIV-positive patients presenting with primary lung cancer, thus, hypothesizing a causal association between HPV infection and SCC.…”

Determining Association between Lung Cancer Mortality Worldwide and Risk Factors Using Fuzzy Inference Modeling and Random Forest Modeling

“…Diet and nutrition, as two of modifiable lifestyle factors, were associated with reduced total cancer-specific mortality, updated by the WCRF and the American Institute for Cancer Research (AICR) (2018) [ 38 , 39 , 40 , 41 ]. Drug use was positively correlated with sexual behaviors [ 42 ], impacting on individual HIV-infection, ultimately resulting in the increased risk of developing lung cancer for the general population [ 43 ]. Unsafe water source is present in various food products, including mutagenic and carcinogenic compounds [ 36 ].…”

Pulmonary squamous cell carcinoma and lymphoepithelial carcinoma – morphology, molecular characteristics and differential diagnosis

“…114,115 Although HPV may play a role in very rare and specific cases of SCC, as in the context of HIV infection and papillomatosis, no HPV association was detected in wellcontrolled studies in conventional SCC. [114][115][116][117][118][119] Also, the presence of PAX8 and CD5 and CD117 (c-Kit) co-expression speak in favour of a thymic origin of the SCC. 120 Molecular analysis may also be utilised, with direct comparison between the extrapulmonary tumour and the pulmonary nodule.…”

“…Subsequently, HPV‐association needs to be validated using an alternative method such as HPV in‐situ hybridisation, as non‐HPV‐associated tumours including lung carcinomas may be aberrantly p16‐positive 114,115 . Although HPV may play a role in very rare and specific cases of SCC, as in the context of HIV infection and papillomatosis, no HPV association was detected in well‐controlled studies in conventional SCC 114–119 . Also, the presence of PAX8 and CD5 and CD117 (c‐Kit) co‐expression speak in favour of a thymic origin of the SCC 120 …”