Biology subjects

Orozco, R.

Publications and source records attributed to Orozco, R..

4 recordsLinked to original sources

bioRxiv2024

Analysis of the progression of cervical cancer in Guatemala- from pre-malignancy to invasive disease

To better understand cervical cancer progression, we analyzed RNA from 262 biopsies from women referred for colposcopy We determined HPV type and analyzed the expression of 51 genes. HPV31 was significantly more prevalent in precancer than stage 1 cancer and invasive cancer (p < 0.0001) and HPV16 increased in invasive disease (p < 0.0001). CCNE1, MELTF, and ULBP2 were significantly increased in HPV16-positive compared to HPV31 precancers while NECTIN2 and HLA-E expression decreased. Markers of the innate immune system, DNA repair genes, and cell cycle genes are significantly increased during cancer progression (p = 0.0001). In contrast, the TP53 and RB1 tumor suppressor gene expression is significantly decreased in cancer cells. TheT cell markers CD28 and FLT3LG expression decreased in cancer while FOXP3, IDO1, and ULBP2 expression increased. There is a significantly higher survival rate in individuals with increased expression of CD28 (p = 0.0005), FOXP3 (p = 0.0002), IDO1 (p = 0.038), FLT3LG (p = 0.026), APOBEC3B (p = 0.0011), and RUNX3 (p = 0.019), and a significantly lower survival rate in individuals with increased expression of ULBP2 (p = 0.035). These results will help us understand the molecular factors influencing the progression of cervical precancer to cancer.

cancer biology↗

bioRxiv2021

Extrachromosomal Amplification of Human Papillomavirus Episomes as a Mechanism of Cervical Carcinogenesis

Integration of Human Papillomaviruses (HPV) is an important mechanism of carcinogenesis but is absent in a significant fraction of HPV16+ tumors. We applied long-read whole-genome sequencing (WGS) to cervical cancer cell lines and tumors. In two HPV16+ cell lines, we identified large tandem arrays of full-length and truncated viral genomes integrated into multiple locations indicating formation as extrachromosomal DNA (HPV superspreading). An HPV16+ cell line with episomal DNA has tandem arrays of full-length, truncated, and rearranged HPV16 genomes (multimer episomes). WGS of HPV16+ cervical tumors revealed that 11/20 with only episomal HPV (EP) have intact monomer episomes. The remaining nine EP tumors have multimer and rearranged HPV genomes. Most HPV rearrangements disrupt the E1 and E2 genes, and EP tumors overexpress the E6 and E7 viral oncogenes. Tumors with both episomal and integrated HPV16 display multimer episomes and concatemers of human and viral sequences. One tumor has a recurrent deletion of an inhibitory site regulating E6 and E7 expression, and another has a recurrent duplication consistent with HPV superspreading. Therefore, HPV16 can cause cancer without integration through aberrant episomal replication, forming rearranged and multimer episomes.

cancer biology↗

bioRxiv2019

High prevalence of precocious menarche in Puerto Barrios, Guatemala

BackgroundAge of menarche is variable between women with a median age of 14 years old worldwide, and averages ranging from 12-13 years old in developed countries to 15-16 years old in low and middle-income countries. Precocious menarche, occurring before age 11, is rare, with a prevalence of 1.4 to 2.3% in most worldwide populations. Precocious menarche is poorly understood but is associated with early puberty and is a risk factor for pre-teen birth. In studying HPV prevalence in Latin America, we identified a community with a very high rate of precocious menarche. Objective(s)Describe the patterns of precocious menarche in Guatemala. Study DesignReproductive histories were collected from 3385 cancer-free women at the time of routine Pap smear from 4 sites in Guatemala including hospitals in Guatemala City and Puerto Barrios, Izabal. Statistical analyses included determination of the age-specific prevalence of menarche and linear regression to determine the effect of year of birth, study site, number of births and miscarriages, on the age at menarche. ResultsCompared with a low prevalence of precocious menarche observed in Guatemala City (3.1%, 88/2834), we observed a high prevalence of precocious menarche in the city of Puerto Barrios, Izabal, Guatemala (88%, 486/551). We observed a high prevalence of precocious menarche in Puerto Barrios across all age groups. In contrast in Guatemala City, the median age at menarche declined from the age of 14 in 50-60-year-old women to 13 in women under 40 years of age. Hospital records show that the occurrence of both miscarriage and pregnancy under age 14 is substantially higher in Izabal. In addition, the main public hospital in Puerto Barrios accounts for a high fraction of the early pregnancies and miscarriages seen in Guatemala. ConclusionsIn Puerto Barrios, Izabal, Guatemala, the prevalence of menarche before age 11 is dramatically elevated compared to Guatemala City and substantially higher than other worldwide populations. We observed precocious menarche in Puerto Barrios in all age groups examined, indicating that this condition has been common for decades. This finding is supported by the comparatively higher occurrence of early pregnancy and miscarriage in Puerto Barrios compared with Guatemala City. The cause is unknown, but precocious menarche is associated with adverse reproductive outcome in young women and warrants further investigation.

epidemiology↗

bioRxiv2017

Low-Cost HPV Screening And The Prevalence Of Cervical Infection In Asymptomatic Populations In Guatemala

BackgroundA low cost and accurate method for detecting high-risk (HR) HPV is important to permit HPV testing for cervical cancer prevention. We validated a low-cost commercially available HPV method (H13, Hybribio, Hong Kong) and determined the distribution of HPV infections in over 1717 cancer-free women in Guatemala.\n\nMethodsH13 results were compared with two more established HPV tests: (Xpert (Cepheid) and SPF10-LIPA25 (DDL)) in 40 mainly known positive specimens. HR-HPV was detected in cervical samples from 1717 cancer-free women receiving Pap smears using the Hybribio realtime PCR assay of 13 HR types. Selected HPV positive samples were sequenced to determine viral type.\n\nResultsThe Hybribio H13 Assay showed 93% identical results with Xpert, and 89% with SPF10-LIPA25. A total of 13% (226/1717) of women tested HPV+. The highest prevalence was found in younger women (<30 years, 22 %) and older ones ([≥]60 years, 15%). The six most common HR-HPV types among the 148 HPV+ typed were HPV16 (22%), HPV18 (11%), HPV39 (11%), HPV58 (10%), HPV52 (8%), and HPV45 (8%).\n\nConclusionsThe Hybribio Assay was low cost, and accurate in testing for HR-HPV infection. As in most places, HPV16 was the most prevalent HR type in Guatemala and the age-specific prevalence curve peaked in younger ages.\n\nHighlightsO_LIA low cost and accurate method, Hybribio Assay, could be used for CC testing in low income regions.\nC_LIO_LIA total of 13% of cancer-free women were HPV+ and positivity was associated with younger age (<30 years old) in Guatemala.\nC_LIO_LIHPV16 was the major prevalent type.\nC_LI

molecular biology↗