# Development of a high-resolution mapping platform for HPV DNA integration in premalignant lesions

> **NIH NIH R21** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $181,613

## Abstract

Abstract
 The vast majority of human cervical cancers are caused by human papillomaviruses (HPVs). These
viruses are also implicated in a fraction of other types of cancer (head & neck, anus, vagina, vulva).
Cervical cancer is the second leading cancer cause of death of women worldwide. Over 40 different types
of HPV infect the genital tract, and nearly half of the human population is infected by an HPV at least once.
However, the vast majority of HPV-infected people infected do not develop invasive tumors due to antiviral
immune responses. Cervical carcinomas develop through a series of cervical intraepithelial neoplasia (CIN)
steps, CIN1, CIN2, and CIN3, but only a minority of women even with CIN3 progress to invasive
carcinomas. The HPV DNA genome replicates as a circular, extra-chromosomal episome with up to many
thousands of copies per infected cell. However, in most invasive carcinomas, HPV DNA is integrated into
human genomic DNA due to aberrant host cell DNA repair mechanisms. This results in the viral oncogenes
(notably E6 and E7) becoming permanently associated with the host cell and its descendents. Usually, the
viral DNA is integrated into a human oncogene, often as only a fraction of the viral genome. Integrated viral
DNA alters oncogene expression resulting in clonal expansion of that cell. Cervical disease has traditionally
been screened and monitored by Pap smears, but HPV testing is proving to have superior specificity and
sensitivity, and is supplanting Pap smears as the primary tool. However, current HPV clinical testing
generally detects only the most common HPV types, and often searches for only a subfraction of the viral
genome. We propose here to develop a method for detection of a massive set of different HPV types
that will succeed even when only a fraction of the viral genome is present. The assay will use
hybridization capture by a DNA probe set for the entire a clade of HPVs (currently 143 types) to enrich for
HPV DNA in tissue samples, followed by deep, next generation DNA sequencing. It will also use a unique
biorepository of cervical CIN1-3, tumor and control samples that we established featuring the highly diverse
Bronx patient population that we serve. In preliminary studies using a 15 HPV type probe set, our method
detected 8 different HPV types in a set of 26 CIN1-3 lesions and tumors, and detected integrated HPV DNA
in 22 of 24 CIN2/3’s and tumors. Our single assay will simultaneously 1) yield unambiguous HPV type
specificity because of the extensive viral sequences obtained, 2) detect common and rare HPV types, 3)
find HPV even when only part of the viral genome is present, 4) determine if integrated HPV DNA is
present, and 5) discern if integrated HPV DNA is near a human oncogene. We further propose to develop a
fluorescence microscopy approach (Junc-FISH) to detect patient-specific integrated HPV in clinical
samples. Our proposed work should provide superior HPV detection methods with higher and much
broader...

## Key facts

- **NIH application ID:** 10250335
- **Project number:** 5R21CA240580-03
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** JACK LENZ
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $181,613
- **Award type:** 5
- **Project period:** 2019-09-16 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10250335

## Citation

> US National Institutes of Health, RePORTER application 10250335, Development of a high-resolution mapping platform for HPV DNA integration in premalignant lesions (5R21CA240580-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10250335. Licensed CC0.

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