PARACHINAR, Pakistan » A suspected U.S. drone carried out a rare missile strike in northwest Pakistan outside the country’s remote tribal region on Thursday, killing five people, including three senior Afghan militants, Pakistani police and intelligence officials said.

The missiles hit an Islamic seminary in Khyber Pakhtunkhwa province’s Hangu district that was known to be visited by senior members of the Afghan Haqqani network, one of the most feared militant groups battling U.S. troops in neighboring Afghanistan, the officials said. One of the militants killed was a deputy of the Haqqani network’s leader.

It was only the second drone attack outside Pakistan’s semiautonomous tribal region along the Afghan border since the strikes began in the country in 2004 and could increase tension between Islamabad and Washington. There was a strike in Khyber Pakhtunkwa’s Bannu district in 2008. Khyber Pakhtunkhwa province is considered a "settled area" of Pakistan, meaning it is generally more populated and developed than the tribal region.

"Now no place is safe. The drones are now firing missiles outside the tribal areas," said Shaukat Yousufzai, health minister for the Khyber Pakhtunkhwa provincial government, which has spoken out strongly against drone attacks.

"It is Hangu today. Tomorrow it can be Karachi, Lahore or any other place," Yousufzai told Pakistan’s Dunya TV.

Pakistan’s Foreign Ministry also protested the strike in a statement sent to reporters, saying the attacks violate the country’s sovereignty.

Thursday’s strike was the first since the U.S. killed former Pakistani Taliban chief Hakimullah Mehsud on Nov. 1 in a missile attack in the North Waziristan tribal area. Pakistani officials were outraged by the attack because they said it came a day before they planned to invite Mehsud to hold peace talks.

The Islamic seminary that was hit was located in the Tall area of Hangu, said district police officer Iftikhar Ahmad. Five people were killed in the attack. No one was seriously wounded, he said.

Pakistani intelligence officials provided the names of five people killed in the strike. One, Ahmad Jan, was a deputy of the Haqqani network’s leader, Sirajuddin Haqqani, they said. Two others were Gul Sher, leader of the Afghan Taliban in Paktia province, and Maulvi Hamidullah, leader of the Afghan Taliban in Khost province, they said. It was unclear whether the other two were militants.

An Afghan intelligence official also confirmed Jan was killed in the attack. A member of the Haqqani network, which is allied with al-Qaida and the Afghan Taliban, confirmed that Jan was one of Sirajuddin Haqqani’s deputies.

The Pakistani and Afghan officials spoke on condition of anonymity because they were not authorized to talk to journalists.

A local TV station showed video footage of the destroyed seminary, which had walls made out of mud and straw. The walls of the room that was targeted were caved in and pockmarked with shrapnel. The rest of the seminary appeared to be intact. The ground outside was littered with shoes and pools of blood. One person held up a piece of metal that appeared to be part of one of the missiles.

Maulvi Noorullah, a teacher at the seminary, said there were nearly 100 students present when the attack occurred. Sixteen students were in the room next to the one that was targeted, but they all survived, he said.

The covert CIA drone program in Pakistan has been a constant source of tension between Islamabad and Washington. Pakistani officials regularly denounce the strikes in public as a violation of the country’s sovereignty. But the government is known to have supported at least some of the attacks in the past. It is generally understood that Pakistan’s secret agreement with the U.S. on drone strikes in the past was confined to the tribal region and did not include the country’s so-called "settled areas."

The Pakistani government has stepped up its opposition to drone attacks since Prime Minister Nawaz Sharif took office in June. Sharif met with President Barack Obama in Washington in October and pressed him to end the strikes. But the U.S. has shown no sign that it intends to stop using what it considers a vital tool to fight al-Qaida and the Taliban.

Imran Khan, the former cricket star who now leads the party that runs the Khyber Pakhtunkhwa government, has called for Pakistan to block trucks carrying supplies to NATO troops in Afghanistan in response to continued drone strikes. The federal government has shown little interest in doing so, but Khan plans to hold a strike on Nov. 23 and block the road through the province that some of the trucks take.

Most drone strikes have occurred in North Waziristan, the headquarters of the Haqqani network in Pakistan. The U.S. has repeatedly urged Pakistan to conduct an operation in North Waziristan, but the government has refused. Many analysts believe Pakistan doesn’t want to cross the Haqqani network, a group with which it has historical ties and could be an ally in Afghanistan after foreign forces withdraw.

Dawar reported from Peshawar. Associated Press writers Riaz Khan in Peshawar contributed to this report.