Invasive cervical cancer is the second most common malignant tumor affecting Brazilian women. The distribution of Human Papillomavirus (HPV) genotypes in Brazil has not been extensively studied. Little is known about the impact of HPV genotypes on invasive cervical cancer survival.
Women with a diagnosis of invasive cervical cancer between November 2008 and July 2012 were recruited from the Instituto do Câncer do Estado de São Paulo (ICESP). DNA was extracted from three 10µM-thick paraffin-embedded cervical carcinoma tissue per subject using the automated BD Viper LT System and high-risk HPV detection and genotyping was determined using the BD Onclarity HPV Assay. Age at diagnosis, clinical staging, histological type and survival data were obtained from the hospital’s electronic data records.
One hundred-ninety-six women with a median age of 51±14 years (range=17-87 years) were studied. Squamous cell carcinoma and adenocarcinoma were diagnosed in 80 and 20% of patients, respectively. Regarding clinical staging (FIGO), 31% were classified as 1A1 to 1B1, 17% as 1B2 to 2A and 52% as 2B to 4A.
The most frequent types were HPV16 (62 %), HPV18 (9%), HPV45 (5%), HPV31 (4%), HPV52 (2%), and others high risk HPV type (18%). Most infections (72%) were caused by individual HPV types, with 28% harboring 2 or more co-infecting types.
There were 66 deaths during up to 118 months of follow-up. Kaplan-Meier survival curves and log-rank statistics revealed that HPV 16/18 (n= 147) did not have a worse prognosis as compared to other HPV types (n=49) (P=0.603). Age at diagnosis, clinical staging, histological type and HPV type were included in a Cox regression model. Only clinical staging was independently associated with survival.
To our knowledge, this is one of the largest studies that assessed HPV genotype from invasive cervical cancer paraffin-embedded tissue samples in Brazil. The present study confirms the continuing major role of HPV16 and 18 in invasive cervical cancer and is similar to other country findings. The observation that more than ¼ of all cancers are caused by non-16/18 types with similar prognosis underlines the importance of extended genotyping in disease detection. Clinical staging at diagnosis was the only predictor of survival, reinforcing the importance of cervical cancer screening and diagnosis at early stages.
1.Cuschieri K, Brewster DH, Graham C, Nicoll S, Williams AR, Murray GI, et al. Influence of HPV type on prognosis in patients diagnosed with invasive cervical cancer. Int J Cancer. 2014;135(11):2721-6.
2.Amaro-Filho SM, Golub JE, Nuovo GJ, Cunha CB, Levi JE, Villa LL, et al. A comparative analysis of clinical and molecular factors with the stage of cervical cancer in a Brazilian cohort. PLoS One. 2013;8(3):e57810.
3.de Oliveira CM, Fregnani JH, Carvalho JP, Longatto-Filho A, Levi JE. Human papillomavirus genotypes distribution in 175 invasive cervical cancer cases from Brazil. BMC cancer. 2013;13:357.
4.Bravo IG, Felez-Sanchez M. Papillomaviruses: Viral evolution, cancer and evolutionary medicine. Evolution, medicine, and public health. 2015;2015(1):32-51.
5.Darus CJ, Mueller JJ. Development and impact of human papillomavirus vaccines. Clinical obstetrics and gynecology. 2013;56(1):10-6.
6.Castellsagué X. Natural history and epidemiology of HPV infection and cervical cancer. Gynecologic oncology. 2008;110(3 Suppl 2):S4-7.