Regular ArticleHuman Papillomavirus Detection of Endometrioid Carcinoma with Squamous Differentiation of the Uterine Corpus
Abstract
Many studies have shown a link between human papillomavirus (HPV) and cervical carcinoma. However, studies on the association of HPV with endometrioid carcinoma of the corpus uteri are sparse and controversial. In this study, 33 formalin-fixed, paraffin-embedded tissue samples of endometrioid carcinoma with squamous cell differentiation in grade 1 (adenoacanthoma) and 10 additional samples of endometrioid carcinoma with less squamous cell differentiation in grade 2 or 3 (adenosquamous carcinoma) were examined by the hybrid capture system for the presence of the 14 most common anogenital HPV types, consisting of low-risk HPV types 6, 11, 42, 43, and 44, and intermediate- and high-risk HPV types 16, 18, 31, 33, 35, 45, 51, 52, and 56. No evidence of high-risk HPV DNA types was found in any of these samples. The low-risk HPV DNA types were found in three samples and showed borderline results (±) in 6 samples by the hybrid capture system. The 43 samples were tested by dot blot hybridization with HPV probes 6/11, 16/18, and 31/33/35. Only 1 sample was positive for HPV 6/11. The results of this study did not indicate an association between HPV infection and endometrioid carcinoma with squamous cells, though the endometrial mucosa of the corpus uteri is anatomically connected to the endocervical epithelium, and in some cases HPV has been postulated to possibly cause squamous cell differentiation of the endometrium. Our findings are in accord with the concept that HPV infection leading to malignancy is highly site- and tissue-specific. In conclusion, the endometrium may not be a suitable host epithelium for HPV replication and maturation.
References (0)
Cited by (32)
Chapter 19 - Adenocarcinoma, Carcinosarcoma, and Other Epithelial Tumors of the Endometrium
2018, Diagnostic Gynecologic and Obstetric PathologyThis chapter addresses new concepts in the prevention, pathogenesis, diagnosis, and management of endometrial epithelial neoplasia. Superimposed on the traditional two disease system (endometrioid and serous carcinomas) is newly discovered molecular subgroups of tumors that correlate with both improved (POLE mutations) and poor (high copy number variation [CNV]) outcomes. Prevention now focuses on more extensive screening for mismatch repair defects by immunohistochemistry to identify a small percentage of patients with a familial predisposition (Lynch syndrome). In practice, the most common classification issues are (1) the identification of subsets of endometrioid carcinomas that are at higher risk for an adverse outcome, including excluding serous carcinoma and (2) distinguishing clear cell carcinoma from clear cell change. Management issues center on determining the depth of invasion, separating real from artifactual vascular space invasion, interpreting nodal micrometastases, and distinguishing metastatic disease from new primary tumors. Ultimately, the role of radiation merits more scrutiny when balancing quality of life with recurrence risk if survival will not be altered. Chemotherapy beyond hormonal therapy remains an ongoing challenge.
Prevalence of Human Papillomavirus in endometrial cancer: A systematic review and meta-analysis
2014, Gynecologic OncologyCitation Excerpt :For all the analyses the statistical software R [23] was used using the packages “meta” [24] and “metafor” [25]. In this systematic review and meta-analysis, we identified 28 papers (29 studies) examining the prevalence of HPV DNA in tumor tissue from endometrial cancer [12,13,26–51]. The studies were published between 1988 and 2013 and comprised altogether 1026 cases of endometrial cancer.
HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.
We conducted a systematic review and meta-analysis to investigate the pooled prevalence of HPV DNA in endometrial cancer. Using meta-regression, we further analyzed whether factors such as geographical region, HPV DNA detection method, publication year and tissue type were associated with HPV prevalence. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for studies providing data on HPV prevalence in cases with endometrial cancer and in controls with normal or hyperplastic endometrial tissue.
We identified 28 papers (29 studies) examining the prevalence of HPV DNA in tumor tissue from endometrial cancer comprising altogether 1026 cases of endometrial cancer. The HPV prevalence varied considerably from 0% to 61.1%. From the random effects meta-analysis, the pooled prevalence of HPV DNA in endometrial cancer was 10.0% (95% CI: 5.2–16.2) with large between-study heterogeneity (I2 = 88.2%, p < 0.0001). The meta-regression showed that HPV DNA detection method was statistically significantly associated with HPV prevalence (p = 0.0016): the pooled HPV prevalence was 6.0% (95% CI: 1.5–13.0) using general primers, 18.9% (95% CI: 8.6–32.1) using type-specific primers and 1.0% (95% CI: 0.0–3.6) using non-PCR based methods. None of the other a priori defined variables were statistically significantly associated with HPV prevalence. The pooled OR was 1.43 (95% CI: 0.68–3.00) indicating that the odds of HPV was not increased in cases versus controls.
HPV appears to have a limited or no role in the etiology of endometrial cancer.
P16<sup>INK4a</sup> overexpression independent of Human Papilloma Virus (HPV) infection in rare subtypes of endometrial carcinomas
2007, Pathology Research and PracticeIn the current study, we evaluated p16 expression in rare subtypes of endometrial carcinomas, whose HPV status has been previously examined in order to establish the role of this protein in their pathogenesis. These rare subtypes of endometrial carcinomas are primary squamous endometrial carcinoma (ESCC), endometrial mucinous microglandular adenocarcinoma (EMMA), and endometrial transitional cell carcinoma (ETCC).
All tissues, obtained at the time of hysterectomy, were fixed in 10% phosphate-buffered formalin and embedded in paraffin. Serial sections were made for hematoxylin and eosin staining and for immunohistochemistry.
Although a previous PCR study has demonstrated that none of these neoplasms showed any signal for HPV DNA, these malignancies did display immunoreactivity for P16INK4a. In ESCC, P16INK4a immunoreactivity was diffuse in 100% of neoplastic cells. In two cases of EMMA, positivity for P16INK4a was zonal. In ETCC, scattered cells were positive for P16INK4a protein.
These findings suggest that alteration of p16 could play an etiologic role, without any association to HPV infections, in these rare endometrial carcinomas.
However, in our view, other cases of these rare malignancies should be investigated in order to confirm this hypothesis.
p16, p14, p53, cyclin D1, and steroid hormone receptor expression and human papillomaviruses analysis in primary squamous cell carcinoma of the endometrium
2006, Annals of Diagnostic PathologyPathogenetically, endometrioid adenocarcinomas of the endometrium are associated with hyperestrogenism and serous papillary carcinomas with alterations of p53. The etiology of primary endometrial squamous cell carcinoma (ESCC), however, is speculative. The purpose of this study was to evaluate the role of p14, p16, p53, cyclin D1, steroid hormone receptors, and human papillomaviruses (HPV) infection in the pathogenesis of primary endometrial squamous cell carcinoma. The expression of p16, p14, p53, cyclin D1, and steroid hormone receptors (estrogen, progesterone, and androgen) was examined immunohistochemically in 8 primary ESCCs. HPV analysis was performed using general primers and HPV typing. The median age of the patients was 62.1 years. Four cases showed positive nuclear and cytoplasmic p16 staining in an insular pattern, and 1 case nuclear positivity for p53 and estrogen receptors, respectively. Four of 8 cases were positive for progesterone receptor analysis and cyclin D1. All cases were negative for p14 and androgen receptor staining. All but one case were negative for HPV analysis. Five patients were alive with and without evidence of disease after a mean follow-up of 6.1 years.
The results of this study suggest that alterations of the p16 pathway may play an etiologic role in at least a proportion of the ESCC, but without any association to HPV infection. Factors known to play a pathogenetic role in types 1 and 2 of endometrial carcinomas are not associated with primary ESCC. However, prognostically, ESCCs are more related to type 1 cancers.
The value of HPV DNA typing in the distinction between adenocarcinoma of endocervical and endometrial origin
2003, PathologyDistinguishing between adenocarcinomas of endocervical and endometrial origin histologically can be difficult, particularly in small biopsies. Most endocervical adenocarcinomas contain human papillomavirus (HPV) deoxyribonucleic acid (DNA) of ‘high-risk’ (HR) types, whereas this has not been consistently demonstrated in endometrial adenocarcinomas. The aim of this study was to determine whether HPV DNA testing could aid in this differential diagnosis.
The frequency of HPV DNA in paraffin-embedded tissue samples from 50 endocervical and 50 endometrial adenocarcinomas was investigated using polymerase chain reaction (PCR) amplification techniques involving (i) a screening HPV test followed by HPV DNA sequencing, and (ii) a test designed to detect HR genotypes 16, 18, 31, 33, 35, 45 and 58. Control specimens included cervical intraepithelial neoplasia (CIN) III lesions, squamous cell carcinomas (SCCs) of the cervix and lung, and colonic adenocarcinomas. Measures to minimise cross-contamination were implemented.
The screening test followed by HPV DNA sequencing had the highest sensitivity. By this test HR HPV DNA was detected in 11 of 11 (100%) cervical intraepithelial neoplasia (CIN III) lesions, nine of 10 (90%) cervical SCCs, none of 10 (0%) colorectal adenocarcinomas and none of 10 (0%) SCCs of the lung. Thirty-nine (78%) endocervical adenocarcinomas contained HR HPV DNA, compared to one (2.0%) endometrial adenocarcinoma.
The results suggest that HPV DNA testing could be a useful adjunct in distinguishing between endocervical and endometrial adenocarcinomas in curettings or small biopsy specimens.
Does human papillomavirus have a role in cancers of the uterine corpus?
1999, Gynecologic OncologyObjective. Thepurpose of this study was to determine the role of the human papillomavirus (HPV) in invasive uterine corpus cancer by characterizing the frequency of HPV DNA in malignant uterine tumors.
Methods. Hysterectomy specimens from 66 women with uterine carcinoma were analyzed. Tumor specimens were frozen at −80°C at the time of surgical resection. DNA was later extracted and examined for HPV DNA using type-specific PCR primers for HPV 6, 16, and 18 and consensus primers MY09/MY11, which detect DNA from 33 other common HPV types. Isolation procedures were undertaken to prevent contamination.
Results. The histologic diagnoses of the 66 uterine cancer cases included 58 endometrial adenocarcinomas, 4 adenosquamous carcinomas, 3 malignant mixed mesodermal tumors, and 1 squamous cell carcinoma. HPV was detected by both type-specific and consensus primers in only 2 of the uterine specimens. None of the typical endometrioid adenocarcinoma specimens contained HPV DNA. HPV 16 was detected in 1 of the adenosquamous carcinoma samples and HPV 18 was detected in the squamous carcinoma specimen.
Conclusion. HPV DNA is not found in malignancies of the uterine corpus without malignant squamous elements when the risk of contamination is minimized. For these tumors, HPV appears to be unrelated to the neoplastic transformation process.