Detection Of HPV(16/18)–Associated Oral Cancer By HPV–E6/E7 Proteins In Saliva

Human papillomavirus(HPV) associated oral squamous cell carcinoma(OSCC) is  distinct entity, whose biological behaviour is different from that of OSCC associated with tobacco habit. Mere presence of HPV in OSCC is not important but  integration of HPV-DNA by E6/E7gene  into  host genome is  important  in development and progression of OSCC. E6/7 genes are more sensitive, detected earlier than L genes for demonstrating HPV. 

Objectives: To determine prevalence of E6/E7 for HPV16 and HPV18 in OSCC in Indian population and to determine whether presence of HPV E6/E7 in saliva can be used as marker for HPV associated OSCC.

Methods: OSCC(n=45)cases were divided into two groups. In group1(n=20) tumour tissue and saliva sample were collected; group2(n=25) comprised of archival tumour tissue samples. Nested-multiplex PCR(NMPCR) was used to detect presence of HPV16 and 18 by demonstration of  E6/E7proteins in tissue and saliva samples.

Results: HPV16and/or18 was present in 50.74%cases,HPV16 was present in 41.79%cases while HPV18 was present in 26.86%cases. With application of Fisher’s exact test at 1% level of significance, there was no significant difference for HPV16and/or18 presence in OSCC tissue and saliva sample indicating that both saliva and tissue can be used to test HPV positivity in OSCC. Taking lesional tissue sample as standard, sensitivity and specificity for total HPV(16/or18) in saliva by NMPCR was estimated at 62.5%(95%CI:61-84%)and 75%(95%CI:73-97%)respectively. Positive predictive value of NMPCR for detection of “HPV16/HPV18” was 62.5% whereas negative predictive value was 75%.

Conclusions: Study reveals moderate level of prevalence of HPV(16/18) in OSCC in Indian population, suggestive of its role in oral carcinogenesis. E6/E7 proteins of HPV(16/18) can be detected from saliva of patients with HPV associated OSCC by NMPCR. As no significant difference in HPV presence was found in lesional tissue and saliva, the presence of E6/E7 proteins in saliva can be used reliably as predictor for HPV positivity in OSCC.