Thursday, January 8, 2026 1/8/2026

Investigations Into The Molecular Pathogenesis Of Cervical Glandular Neoplasias

Award Number: U01CA238592
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/02/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Investigations Into The Molecular Pathogenesis Of Cervical Glandular Neoplasias - ABSTRACT More than 12,000 women are diagnosed with cervical cancer, an HPV-associated malignancy, annually in the U.S. There are two major histologic forms of cervix cancer: squamous cell carcinoma (SCC) and adenocarcinoma (ADENO). Importantly, SCC can be prevented through cervical cytology screening programs, whereas ADENO cannot. While there is a prophylactic vaccine against HPV, uptake of HPV vaccination in the U.S. has been poor and there are several generations of women who are already exposed to HPV infection and will not be helped by HPV vaccination. Therefore, cervical screening at a cost of over $6 billion per year will be needed for several decades at least. Understanding the molecular pathogenesis of ADENO has important public health value in order to facilitate the prevention of ADENO, for which current screening strategies are inadequate. In the US and Europe, HPV16, 18, and 45 infections account for >95% of AIS/ADENO. We examined viral methylation of HPV16/18/45 AIS (n=27) and cervical intraepithelial neoplasia grade 3 (CIN3) (n=63) cases compared to 90 HPV16/18/45 control infections with <CIN2, and found AUC's of 0.99 and 0.82 for HPV16, respectively. In addition, we have preliminary data showing that methylation levels of a host gene panel is significantly higher in AIS lesions (p<0.001) compared to controls (<CIN2). Furthermore, we have employed an HPV-DNA capture NGS assay to prospectively evaluate viral integration and found a specific HPV18 viral integration that is maintained for the entirety of the screening. We further found that this integration site has a progressive increase in HPV-integration reads leading up to, and with a dramatic spike in coverage directly preceding, the histological identification of an incident CIN3 lesion. The NGS detected integration likely represents an expanding malignant cell clone and shows strong potential for clinical application. We propose to investigate the natural history of HPV and ADENO precursors (i.e., samples prior to the diagnosis of ADENO and from AIS) with the goal of defining molecular precursors of ADENO, which could be amenable to immediate treatment and thus prevent ADENO. We will leverage cohorts with large numbers of HPV16, 18, and 45-positive women (n > 20,000) in whom the vast majority of ADENO occur, to measure host and HPV viral methylation changes and HPV viral integration to molecularly define the natural history of ADENO. We will compare and contrast these findings with the better known natural history of SCC. Ultimately, we will develop a risk-prediction model for AIS/ADENO precursors using HPV genotypes, HPV viral and host gene epigenetics, and HPV viral integration.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$4 )
2026	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cancer Cause and Prevention Research	000	5	12/4/2025	NON-COMPETING CONTINUATION	-$4
														Subtotal = -$4

Issue Date FY: 2024 ( Subtotal = $516,029 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cancer Cause and Prevention Research	000	5	6/12/2024	NON-COMPETING CONTINUATION	$516,029
														Subtotal = $516,029

Issue Date FY: 2023 ( Subtotal = $571,572 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cancer Cause and Prevention Research	000	4	7/7/2023	NON-COMPETING CONTINUATION	$571,572
														Subtotal = $571,572

Issue Date FY: 2022 ( Subtotal = $571,574 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cancer Cause and Prevention Research	001	3	6/23/2022	NON-COMPETING CONTINUATION	$571,574
2022	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cancer Cause and Prevention Research	000	2	2/3/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $571,574

Issue Date FY: 2021 ( Subtotal = $583,239 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cancer Cause and Prevention Research	000	2	7/1/2021	NON-COMPETING CONTINUATION	$583,239
														Subtotal = $583,239

Issue Date FY: 2020 ( Subtotal = $559,479 )
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cancer Cause and Prevention Research	000	1	7/2/2020	NEW	$557,053
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Cancer Cause and Prevention Research	001	1	7/6/2020	NEW	$2,426
														Subtotal = $559,479

Grand Total All Awards = $2,801,889

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Investigations Into The Molecular Pathogenesis Of Cervical Glandular Neoplasias

Award Number: U01CA238592

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/02/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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