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Cervical cancer (CC) continues to be a major public health problem in Mexico, ranking second among cancers in women. A persistent infection with human papillomaviruses (HPV) is the main risk factor for CC development. In addition, a significant fraction of other cancers including those of the anus, oropharynx, and penis are also related to HPV infection. In CC, HPV-16 is the most prevalent high-risk HPV type, followed by HPV-18, both being responsible for 70% of cases. HPV intratype variant lineages differ in nucleotide sequences by 1-10%, while sublineages differ by 0.5-1%. Several studies have postulated that the nucleotide changes that occur between HPV intratype variants are reflected in functional differences and in pathogenicity. Moreover, it has been demonstrated that HPV-16 and -18 intratype variants differentially affect molecular processes in infected cells, changing their biological behavior that finally impacts in the clinical outcome of patients. Mexico has participated in providing knowledge on the geographical distribution of intratype variants of the most prevalent HPVs in premalignant lesions of the cervix and cervical cancer, as well as in other HPV-related tumors. In addition, functional studies have been carried out to assess the cellular effects of intratype variations in HPV proteins. This review addresses the state of the art on the epidemiology of HPV-16 and HPV-18 intratype variants in the Mexican population, as well as their association with persistence, precancer and cervical cancer, and functional aspects related to their biological behavior.

Background: Human papillomavirus infection is an important factor associated with cervical cancer (CC) development. The prevalence and genotype distribution vary greatly worldwide. Examining local epidemiological data constitutes an important step towards the development of vaccines to prevent CC. In this work, we studied the prevalence of HPV genotypes in women from Western Mexico with the COBAS 4800 and/or Linear Array Genotyping Test (LA)., Methods: The samples analysed in this study represent a population from Western Mexico, which includes six different states. Our approach was first to test for HPV in cervical samples from women who attended their health clinic for routine gynaecological studies (open-population, n = 3000) by utilizing COBAS 4800. Afterwards, 300 of the HPV-positive samples were randomly selected to be genotyped with LA; finally, we genotyped samples from women with cervical intraepithelial neoplasia grade 1 (CIN 1, n = 71) and CC (n = 96) with LA. Sociodemographic data of the diverse groups were also compared., Results: The overall HPV prevalence among the open-population of women as determined by COBAS 4800 was 12.1% (n = 364/3000). Among the HPV-positive samples, single infections (SI) with HPV16 were detected in 12.4% (n = 45/364), SI with HPV18 were detected in 1.4%, and infection with at least one of the genotypes included in the high-risk HPV pool was detected in 74.5% of the cases. LA analysis of the samples showed that in addition to HPV genotypes 16 and 18, there was a high prevalence of HPV genotypes 59, 66, 52, 51, 39 and 56 in women from Western Mexico. With respect to the sociodemographic data, we found statistically significant differences in the number of pregnancies, the use of hormonal contraceptives and tobacco intake., Conclusions: Our data indicate that there is a high prevalence of HPV genotypes which are not covered by the vaccines currently available in Mexico; therefore, it is necessary to include HPVs 59, 66, 51, 39 and 56 in the design of future vaccines to reduce the risk of CC development. It is also essential to emphasize that the use of hormonal contraceptives and tobacco smoking are risk factors for CC development in addition to the presence of HPV.

Importance: Triage tests enhance the efficiency cervical cancer screening based on human papillomavirus (HPV), but the best approach for maximizing programmatic effectiveness is still uncertain, particularly in a real-world scenario., Objective: To compare the clinical performance of 6 triage strategies based on liquid-based cytology (LBC) and HPV-16 and HPV-18 genotyping individually or in combination as sequential triage tests to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher among women with high-risk HPV., Design, Setting, and Participants: This diagnostic study of routine cervical cancer screening was conducted at 100 primary health centers in Tlaxcala, Mexico. Women aged 30 to 64 years were recruited from August 1, 2013, to February 24, 2016, as part of the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage study. Six triage scenarios for referral to colposcopy were examined: (1) LBC testing that found atypical squamous cells of undetermined significance (ASC-US) or worse, (2) positive results in HPV-16 genotyping, (3) positive results in HPV-18 genotyping, (4) positive results in HPV-16/HPV-18 genotyping, (5) positive results in HPV-16 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse, and (6) positive results in HPV-16/HPV-18 genotyping or, if genotyping results were negative, reflex LBC testing that found ASC-US or worse. Data were analyzed from October 2017 to August 2018., Exposures: Liquid-based cytological testing with simultaneous HPV-16 and HPV-18 genotyping. Women whose HPV genotyping results were positive for HPV-16 or HPV-18 or whose LBC results found ASC-US or worse and a random set of negative and normal results were referred to colposcopy with histologic analysis used for disease confirmation., Main Outcomes and Measures: Clinical performance of each test strategy for detection of CIN grade 2 or higher. Secondary outcomes included resource utilization of each triage scenario, measured by the number of tests performed, the referral rate for colposcopy, and the numbers of colposcopies per CIN grade 2 or higher detected., Results: A total of 36 212 women (median [interquartile range] age, 40 [35-47] years) were screened, and 4051 women (11.2%) had high-risk HPV. Of these women, 1109 (24.6%) were found to have HPV-16, HPV-18, or ASC-US or worse. Further histologic testing detected CIN grade 2 or higher in 110 of 788 women (14.0%) who underwent follow-up colposcopy. Sensitivity and specificity for 3 main triage strategies were 42.9% and 74.0% for LBC; 58.3% and 54.4% for HPV-16/HPV-18 genotyping; and 86.6% and 34.0% for HPV-16/HPV-18 genotyping with reflex LBC. The referral rate to colposcopy was 29% for HPV-16/HPV-18 with reflex LBC, which was 2-fold higher than the referral rate of 12% for LBC., Conclusions and Relevance: Triage of women with high-risk HPV with HPV-16/HPV-18 genotyping with reflex LBC was significantly associated with improvement in detection of CIN grade 2 or higher compared with LBC alone. The benefit of disease prevented may outweigh the cost of increasing requirements for colposcopy services in settings with limited adherence to follow-up after a positive screening result.

Background: Vigilant management of women with high-risk human papillomavirus (hrHPV) is necessary in cancer screening programs. To this end, we evaluated the performance of S5 (targeting DNA methylation in HPV16, HPV18, HPV31, HPV33, and human gene EPB41L3) to predict cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in a sample of hrHPV-infected women referred to colposcopy in the FRIDA Study, a large screening trial in Mexico. A nested case-control sample with women referred to colposcopy either by atypical squamous cells of undetermined significance or higher (ASCUS+) in cytology and/or positive for HPV types 16 or 18 was tested by S5. Seventy-nine cases of CIN2+ were age-matched to 237 controls without a diagnosis of CIN2+ (

Background: The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico., Materials and Methods: DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC., Results: Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association., Conclusions: The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.

Background: Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma., Methods: Mastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995-2008). Demographic and clinical information was obtained from patients' medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher's exact tests, as appropriate., Results: High-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24-72 years), the same as for HPV-negative cases (range, 30-73 years). There were not striking differences between HPV + and HPV- metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR)., Conclusions: High-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones, as so the HPV viral loads; notwithstanding, HPV viral loads show wide variation and remain even lower than cervical and other non-cervical carcinomas, making it difficult to assume that HPV could play a key role in breast carcinogenesis. Further studies are warranted to elucidate the meaning of the presence of high-risk HPVDNA in breast carcinomas.

Persistent infection with human papillomavirus (HPV) has been recognized as the main etiological factor of morbimortality in cervical cancer. Several factors have been associated with the development of cervical disease, but viral load has recently been proposed as an indicator of cervical neoplasia. Therefore, a single measurement of viral load could be a suitable biomarker. We examined HPV viral load as a prognostic biomarker of cervical neoplasia. We used cervical scrapes to determine the total HPV viral load of 46 Mexican patients with various stages of cervical intraepithelial neoplasia (CIN) using hybrid capture assay coupled with a quantitative polymerase chain reaction method for cellularity estimation. Viral load values of CIN2 and CIN3 samples were compared with samples without cervical pathology (WP); all values of viral load were normalized by number of cells analyzed. The analysis showed significant differences in viral load between CIN2 and WP samples (P = 0.01) and between CIN3 and WP samples (P = 0.02). By contrast, no significant difference was detected between viral loads in CIN2 and CIN3 samples. The results showed significant difference between viral loads in CIN2 and CIN3 samples and that in WP samples. HPV viral load was significantly different between patients with CIN2-CIN3 and those with WP and can be used as a predictor of lesions.

Background: The aim of the present study was to determine the association of high-risk human papillomavirus (HR-HPV) in Mexican individuals with oral squamous cell carcinoma (OSCC) and their association with various risk factors., Methods: We designed a matched case-control study. Cases were individuals with newly diagnosed OSCC, age- and sex-matched with controls (1:4). Demographic and clinical data were obtained; also a self-administered questionnaire about sexual behavior was included. DNA from oral brushing was purified to amplify HPV-DNA through MY09/MY11 and GP5+/GP6+ primers and subsequently subjected to sequencing. Conditional regression models were built to calculate odds ratios (ORs) and 95% confidence intervals (CI)., Results: Sixty two cases and 248 controls (53.2% males), median age 62 years (Q1-Q3=54-72 years) were included. HPV prevalence was 43.5% in cases and 17.3% in controls (HR-HPV: 37.1% cases, 9.7% controls). The most frequent types in cases were HPV-16 and HPV-18 (55.6 and 18.5%). The presence of HR-HPV was associated with OSCC (OR=6.2; 95% CI: 2.98-12.97) controlling for the most common risk factors. An interaction between smoking and drinking was detected, and family history of cancer was also significant (OR: 3.61; 95% CI=1.44-8.99). Early age at first sexual intercourse and large number of lifetime sexual partners showed an association with HR-HPV (p=0.019 and p=0.033, respectively)., Conclusions: Oral HR-HPV was strongly associated with OSCC, suggesting that HPV-16 and -18 are risk factors for oral cancer in Mexican patients. A significant association of tobacco and alcohol was confirmed. In addition, family history of cancer was associated with OSCC. The results underline the role of HPV in OSCC and its multifactorial etiology.

The presence of human papillomavirus (HPV) genome in lung carcinomas has been reported worldwide but its frequency varies from country to country. We examined HPV genome in 36 lung carcinomas, consisting of 14 squamous cell carcinomas, 13 adenocarcinomas, and 9 small cell carcinomas, collected from Colombia, Mexico and Peru. PCR analysis using GP5+/GP6+ primers, combined with Southern blot hybridization, found the presence of HPV genome in 10 (28%) of 36 cases. This percentage is similar to the value of 22% reported by Syrjänen, who conducted a meta-analysis of nearly 2500 lung carcinomas examined to date. Genotype analysis revealed that the most predominant genotype was HPV-16 (7 cases), followed by HPV-18 (2 cases) and HPV-33 (1 case). HPV-16 was more frequently found among female than male cases (P=0.008) but was not detected in any adenocarcinoma cases. On the other hand, HPV-18 and HPV-33 were detected only among male cases. These HPV genotypes were detected only in adenocarcinomas, and all the HPV genotypes detected in this histological type were HPV-18 or HPV-33. The frequency of HPV-16 positive cases among all the HPV positive cases differed in the sexes (P=0.033) and differed in the three histological types (P=0.017). The presence of HPV tended to be more frequent in well-differentiated tumors when squamous cell carcinomas and adenocarcinomas were combined. However, it was not statistically significant (P=0.093). Neither p16 nor p53 expression in carcinoma cells was related to the proportion of HPV-positive cases. In conclusion, high-risk HPV DNA was detected in 28% of lung carcinomas. The predisposition of HPV-16 to female cases and to non-adenomatous carcinomas warrants further investigation.