Dr. Hoang is an Anatomical Pathologist and Clinical Assistant Professor at Vancouver General Hospital and the University of British Columbia, offering subspecialty expertise in gynecologic pathology. She completed her pathology training at the University of British Columbia and fellowship training in gynecologic pathology at Memorial Sloan Kettering Cancer Center in New York. In her early career, she has helped to refine the molecular underpinnings of a novel form of uterine sarcoma and push the traditional histologic classification scheme of endometrial carcinoma towards a molecular-based model. Currently, her research is centered on improving diagnostic techniques and treatment strategies for HPV-independent cancers of the female lower genital tract (vulva and cervix), which represent understudied and under-recognized diseases with important clinical ramifications.
Cervical cancer is the fourth leading cancer in women, with an age-standardized incidence of 13 per 100,000 women globally, and highest cause of cancer-related death among women in some countries. The absolute number of cases has been increasing over time, with almost 0.6 million cases and 0.3 million deaths a year in 2018. The majority of cervical cancers are squamous cell carcinomas, which are overwhelmingly attributed to human papillomavirus (HPV). The other major group of cervical cancers are adenocarcinomas (10-20% of total cervical cancers) which unlike their squamous counterparts, have significant proportions of both HPV-associated (HPVA) (~80%) and non-HPV-associated (NHPVA) neoplasms (~20%). NHPVA cervical adenocarcinomas (ECAs) have worse outcomes than HPVA adenocarcinomas, similar to other HPV prone organ sites such as the vulva and oropharynx. The classification of endocervical ECA however, like many traditions in pathology, still relies heavily on morphologic features, without adequately incorporating etiology or clinical relevance.
The existing classification system for cervical adenocarcinomas from the World Health Organization (WHO) is based solely on morphologic characteristics under the microscope. It is a confusing classification system, where each group has unclear definitions, variable associations with HPV infection and no direct relationship to clinical or treatment outcomes. Currently, cervical adenocarcinomas are all treated the same, even though they are a heterogeneous group of tumors. Major advancements in classifications for endometrial and ovarian cancer have been made due to the integration of molecular information, which has led to the development of tailored treatment strategies. Cervical adenocarcinoma, in contrast, has been left behind.
We have been working on a new classification system for cervical adenocarcinomas, called the International Endocervical Adenocarcinoma Criteria and Classification (IECC), created by a group of gynecologic subspecialty pathologists from around the World. The IECC shows improved reproducibility over the WHO system and is supported by HPV-status and clinical features. We are investigating the molecular landscape of ECA under the new IECC and working to develop better biomarkers for the more aggressive and difficult to recognize NHPVA ECA group.
Stolnicu S, Barsan I, Hoang L, Patel P, Terinte C, Pesci A, et al. International Endocervical Adenocarcinoma Criteria and Classification (IECC): A New Pathogenetic Classification for Invasive Adenocarcinomas of the Endocervix. Am J Surg Pathol. 2018 Feb;42(2):214-226.
Stolnicu S, Hoang L, Soslow RA. Recent advances in invasive adenocarcinoma of the cervix. Virchows Arch. 2019 Nov;475(5):537-549.
Stolnicu S, Hoang L, Chiu D, et al. Clinical Outcomes of HPV-associated and Unassociated Endocervical Adenocarcinomas Categorized by the International Endocervical Adenocarcinoma Criteria and Classification (IECC). Am J Surg Pathol. 2019 Apr;43(4):466-474.
Squamous cell carcinoma is by far the most common cancer in the vulva, accounting for more than 90% of tumors in the anogenital region. The precursor lesion to invasive SCC in the vulva is termed vulvar intraepithelial neoplasia (VIN). VIN is divided into two major types based on its etiology: 1) Usual VIN (uVIN), which is driven by human papillomavirus (HPV) infection, and 2) Differentiated VIN (dVIN), which occurs independent of HPV-infection.
On tissue biopsy, the histologic features of uVIN are easy to recognize, while the diagnosis of dVIN is much more difficult. As a result, a patient may undergo multiple biopsies which are diagnosed as non-specific or benign, before a diagnosis of dVIN is made. This is important because the window of opportunity for early surgical intervention and cure is often gone before dVIN is recognized on histology. As one can image, surgical excision for vulvar carcinoma (vulvectomy) can cause significant morbidity, attributed to both the procedure (which may cause significant lymphedema and deformity) and the psychological/sexual distress related to tumors in the anogenital region. It is not uncommon for elderly women, who are most affected by dVIN, to present with advanced stage disease, as some patients are often too embarrassed to seek medical attention early on. dVIN is a biologically aggressive lesion, and thus early intervention is paramount to improving patient outcomes. Compared to uVIN, dVIN is 6-times more likely to progress to invasive SCC and progresses to invasive carcinoma twice as fast.
To further the problem, there are no robust biomarkers that pathologists can use to make the diagnosis. Our research goals are to develop better biomarkers to allow for earlier diagnosis and treatment, and develop better treatment strategies for these patients, using genomic, transcriptomic, and proteomic strategies.
Hoang LN, Park KJ, Soslow RA, Murali R. Squamous precursor lesions of the vulva: current classification and diagnostic challenges. Pathology. 2016 Jun;48(4):291-302.
Tessier-Cloutier B, Kortekaas KE, Thompson E, Pors J, Chen J, Ho J, et al. Major p53 immunohistochemical patterns in in situ and invasive squamous cell carcinomas of the vulva and correlation with TP53 mutation status. Mod Pathol. 2020 Aug;33(8):1595-1605.
Tessier-Cloutier B, Pors J, Thompson E, Ho J, Prentice L, McConechy M, Aguirre-Hernandez R, Miller R, Leung S, Proctor L, McAlpine JN, Huntsman DG, Gilks CB, Hoang LN. Molecular characterization of invasive and in situ squamous neoplasia of the vulva and implications for morphologic diagnosis and outcome. Mod Pathol. 2020 Aug 13. doi: 10.1038/s41379-020-00651-3. Online ahead of print. PMID: 32792599
Thompson EF, Chen J, Huvila J, Pors J, Ren H, Ho J, et al. p53 Immunohistochemical patterns in HPV-related neoplasms of the female lower genital tract can be mistaken for TP53 null or missense mutational patterns. Mod Pathol. 2020 Sep;33(9):1649-1659.