The incident took place around 2 pm when people attended Friday prayers at the mosque in the Haska-Mena district, Nangarhar Police spokesperson Mubariz Atal told Efe news.
"Initial information shows 16 civil have been martyred and over 40 injured in an explosion," he said.
The number of victims could rise in the next few hours due to the mosque being crowded, Atal said, adding that initial information suggested that the explosion could have been caused by the impact of a mortar hitting the building's roof.
However, spokesperson for the regional Governor Attaullah Khogyanai said in a statement that there had been an explosion inside the mosque.
"Due to the explosion, the roof of the mosque collapsed and tens of people were killed and injured," he said.
No group has claimed the attack in Nangarhar a province where both the Taliban and the Islamic State have a presence.
The attack comes a day after the United Nations Assistance Mission in Afghanistan said in a report that violence has been rising in the country in recent months.
Between July and September, 1,174 civil were killed and 3,139 were injured, which amounts to the highest civilian casualties in a quarter (three-months period) since the UNAMA began keeping records in 2009.
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( With inputs from IANS )