Clinical implications of human papillomavirus genotype in cervical adeno-adenosquamous carcinoma
Introduction
Cervical carcinoma is the third most common cancer among women worldwide.1 Thanks to the Pap smear screening, the overall incidence rates of invasive cervical carcinoma are decreasing, while trends showing an increasing ratio of glandular cancers have been noted in the United States (US) and in Taiwan.2, 3 A study of cervical adenocarcinoma (AD) incidence rates in Europe found a decline in period-specific rates in the United Kingdom, Denmark and Sweden with a general increase in other countries.4
A meta-analysis of eight pooled case-control studies found that the adjusted odds ratio for cervical AD or adenosquamous carcinoma (ASC) in human papillomavirus (HPV)-positive women compared with HPV-negative was 81.3 (95% confidence interval = 42.0–157.1).5 Although AD/ASC shares many common risk factors including HPV infections with squamous carcinoma (SC) except smoking,6 tumour gene expression profile and biology of different histologic types seems different in some ways.7, 8 Whether AD/ASC should be treated differently from SC has been controversial.8, 9 Previous studies indicated that AD/ASC histology and metastasis to lymph nodes were risk factors for poor outcome regardless of primary irradiation or surgery.8, 10
HPV18 or alpha-7 species were over-presented in AD/ASC rather than SC in previous studies.11, 12 HPV18 has also been confirmed as a significant prognostic factor in invasive cervical cancers (SC and AD/ASC together) after adjusting for confounding factors.13, 14, 15, 16 However, AD/ASC comprised 10–24.1% of all cervical cancers8, 9; whether HPV genotype independently impacts on outcome was not clear.
The aims of this study were to evaluate the distribution of HPV genotype and the correlation between HPV parameters and clinicopathological/treatment variables and prognostic factors including HPV variables in cervical AD/ASC patients treated between 1993 and 2008. Prognostic modelling was constructed and followed by internal validation.
Section snippets
Study population
Consecutive patients who underwent primary definitive surgery or radiotherapy (RT) for invasive cervical carcinoma of FIGO stages I–IV between 1993 and 2008 at Chang Gung Memorial Hospital were retrospectively reviewed. Formalin-fixed paraffin-embedded tissue specimens were used for DNA analysis. Eliminating those who had a wrong diagnosis or incomplete medical records, with missing paraffin blocks, and with inadequate DNA quality, the remaining patients were eligible for the HPV genotype study.
Patient characteristics
A total of 491 patients with cervical AD/ASC were retrieved from tumour registry, however 34 patients were not eligible for coding error (endometrial cancer, vaginal cancer or SC coded as AD/ASC). A total of 456 AD/ASC patients were eligible for HPV DNA analysis. Four patients untreated after diagnosis or with coexisting other advanced cancer were excluded for survival analysis, and the remaining 452 were eligible. Among the 2118 cervical cancer tissue specimens (1993–2000), 72 were
Discussion
In the literature, HPV-positivity in AD/ASC tumours varied widely from 62.6% to 96.9%, and HPV16/18 comprised 63-93.8%.11, 12, 23 A meta-analysis of 11,878 SC and 2521 AD/ASC cases with HPV type-specific prevalence data pooled found that HPV DNA was detected in 80.3% as compared with SC (90.1%). HPV18 comprised 37.9% and HPV16 comprised 35.3%.12 In our study, HPV DNA sequences were detected in 95.6% of the AD/ASC specimens. AD/ASC harboured HPV16 or HPV18 significantly more common (80.8%) than
Grand supports
Supported by Grants from the National Science Council-Taiwan (NSC94-2314-B-182-011 and NSC97-2314-B-182-013-MY3), Chang Gung Medical Foundation (CMRPG380441-2), and the Department of Health, Taiwan (DOH99-TD-B-111-005 and DOH100-TD-B-111-005).
Role of funding source
Chang Gung Medical Foundation and the Department of Health-Taiwan were not involved in the design of the study, collection, management, analysis or interpretation of the data, preparation, review or approval of the manuscript.
Conflict of interest statement
None declared.
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2022, Taiwanese Journal of Obstetrics and GynecologyCitation Excerpt :Meanwhile, some of the sites also participated prospective collection of AD/ASC patients' fresh tumor tissue and blood sample after signing IRB approved informed consent since October 2014 till May 2020. The cases enrolled retrospectively from Chang Gung Memorial Hospital, Linkou Branch were between January 2009 and July 2014 because the cases 1993 to 2008 were analyzed and published previously [9]. Those who had a wrong pathology report (squamous carcinoma, neuroendocrine small cell or large cell carcinoma, cannot rule out endometrial origin (by immunohistochemistry and imaging studies), and incomplete medical records were excluded from the study.
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2017, Taiwanese Journal of Obstetrics and GynecologyCitation Excerpt :In spite of a well-organized public cervical screening program, correct education to healthcare providers and the population are necessary for the success of cervical cancer prevention [8]. Thus, further education regarding Pap smear screening and cervical cancer is important for the general population, especially in women who have never had a Pap smear, and low-income or at-risk groups [31,32]. Our study showed that women with ADC were younger and had a regular Pap smear screening history.
Prognostic factors and adjuvant therapy on survival in early-stage cervical adenocarcinoma/adenosquamous carcinoma after primary radical surgery: A Taiwanese Gynecologic Oncology Group (TGOG) study
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