Significance of HPV16 Viral Load Testing in Anal Cancer

Abstract

Human papilloma virus (HPV) is highly frequent among patients with anal squamous cell carcinoma, but the viral load (VL) differs between patients. This study aimed to compare the rate of HPV positivity, HPV16VL, p16 INK4A and p53 expression between treatment naive and recurrent anal cancer patients. HPV was genotyped via AmpliSens® HPV HCR-genotype-titre-FRT kit. HPV16 VL was determined via quantitative polymerase chain reaction-based in-house test. p16 INK4A and p53 expression was tested via immunohistochemistry. The cohort comprised 13 treatment-naive and 17 recurrent anal SCC patients. High-risk HPV was detected in 87% of cases, and HPV16 (73%) was the predominant genotype. The rate of HPV positivity was higher among women and nonsmokers, and majority of HPV-positive cases were also p16 INK4A-positive. All p53-negative tumors were HPV16-positive. The most predominant p53 staining pattern in the HPV-positive group was scattered type, whereas it was diffuse type in the HPV-negative group. The HPV16 VL was higher in the treatment-naive group. Further, in the treatment-naive group, cases with scattered staining pattern of p53 had higher HPV16 VL than cases with diffuse staining pattern. The opposite result was noted in the recurrent cancer group. Moreover, p16-positive cases with scattered p53 staining pattern in the treatment naive group had higher HPV16 VL than their counterparts in the recurrent cancer group. In conclusion, the HPV VL, as is the association between VL and p16 INK4A /p53, is in an inversed trend in treatment naive and recurrent cancer patients, highlighting the importance of HPV VL measurement in anal SCC.

HPV status and HPV16 viral load in anal cancer and its association with clinical outcome

“…Complimentary studies have investigated the implications of HPV viral load in and around the anal canal, 28‐32 however, the majority of the available publications have looked into HPV load in people living with HIV. Other studies have assessed VL in anal cancer 31,32 and found a median of 7.40 and 134 copies/cell. However, to our knowledge only one investigation has explored the association between HPV load, local control of cancer and overall survival 31 .…”

“…Complimentary studies have investigated the implications of HPV viral load in and around the anal canal, 28 , 29 , 30 , 31 , 32 however, the majority of the available publications have looked into HPV load in people living with HIV. Other studies have assessed VL in anal cancer 31 , 32 and found a median of 7.40 and 134 copies/cell. However, to our knowledge only one investigation has explored the association between HPV load, local control of cancer and overall survival.…”

“…However, to our knowledge only one investigation has explored the association between HPV load, local control of cancer and overall survival. 31 Authors found that patients with HPV16 DNA VL below the median viral load with low p16 expression showed significantly worse local control and overall survival (OS) than those with a VL above median. 32 …”

Detection of human papillomavirus, viral load and risk factors in patients with precancerous diseases and malignant neoplasms in St. Petersburg

“…В нашем исследовании при анальном раке и РШМ ВПЧ ВКР выявлен во всех образцах, что согласуется с данными, опубликованными ранее зарубежными авторами об этиологическом сходстве возникновения РШМ и анального рака [3,12,21]. Средняя величина вирусной нагрузки (5,7-5,8 lg ДНК ВПЧ/10 5 клеток) при III-IV стадиях рака анального канала, РШМ и HSIL подтверждает гипотезу, что большое число копий генома ВПЧ увеличивает вероятность интеграции вирусной ДНК в геном хозяина, что может играть роль в канцерогенезе инвазивного рака и прогрессировании заболевания [19,20].…”

“…Уровень ВПЧ-позитивности выше среди женщин. При исследовании вирусной нагрузки ВПЧ 16 выявлено, что она была выше в группе больных, ранее не получавших лечения [19]. Установлено, что ВПЧ-позитивность была связана с лучшей выживаемостью и ответом на химио лучевую терапию (подобно плоскоклеточному раку головы и шеи), а низкая вирусная нагрузка была прогностическим фактором более низкой общей выживаемости [1,17].…”